WorldWideScience

Sample records for syndrome brain overgrowth

  1. Genetic syndromes associated with overgrowth in childhood

    Directory of Open Access Journals (Sweden)

    Jung Min Ko

    2013-09-01

    Full Text Available Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future.

  2. Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons from Patient-Derived IPS Cells

    Science.gov (United States)

    2015-12-01

    We recruited 8 ASD patients with quantitative MRI-validated early brain enlargement ranging from mild to macrencephaly and 5 age/ gender -matched...Award Number: W81XWH-13-1-0415 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS...pathogenesis: early brain overgrowth and synaptogenesis defects. The goal of this project is to produce human cellular models of non-syndromic ASD. We used

  3. The Weaver syndrome: a rare type of primordial overgrowth.

    Science.gov (United States)

    Majewski, F; Ranke, M; Kemperdick, H; Schmidt, E

    1981-11-01

    A boy with primordial overgrowth, macrocephaly, and anomalies of the face, nails, feet and skeleton is reported. Two cases in the literature- referred to as Weaver syndrome- exhibited nearly identical anomalies. All three cases were sporadic. Main symptoms of the Weaver syndrome are increased birth weight, early overgrowth, macrocephaly, accelerated osseous maturation, typical facies, hoarse, low pitched voice, hypertonia of muscles and mild developmental delay. Further symptoms are thin, deep-set nails, talipes equinovarus, widened distal femora, and some minor abnormalities. A second boy with primordial overgrowth and macrocephaly demonstrated some, but not all, the symptoms of this syndrome. Whether this boy showed a milder expression of the Weaver syndrome or benign familial macrocephaly is discussed.

  4. Mental deficiency, alterations in performance, and CNS abnormalities in overgrowth syndromes.

    Science.gov (United States)

    Cohen, M Michael

    2003-02-15

    Mental deficiency, alterations in performance, and central nervous system (CNS) abnormalities are discussed in the following overgrowth syndromes: Sotos syndrome, Weaver syndrome, Proteus syndrome, neurofibromatosis type 1, fragile X syndrome, syndromes with neonatal hypoglycemia, Simpson-Golabi-Behmel syndrome, hemihyperplasia, Sturge-Weber syndrome, Bannayan-Riley-Ruvalcaba/Cowden syndrome, macrocephaly-autism syndrome, PEHO syndrome, chromosomal syndromes, and other miscellaneous syndromes. Copyright 2003 Wiley-Liss, Inc.

  5. Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome

    NARCIS (Netherlands)

    van Asperen, C. J.; Overweg-Plandsoen, W. C.; Cnossen, M. H.; van Tijn, D. A.; Hennekam, R. C.

    1998-01-01

    The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1

  6. Small Intestinal Bacterial Overgrowth is Associated with Intestinal Inflammation in the Irritable Bowel Syndrome.

    Science.gov (United States)

    David, Liliana; Babin, Alexandru; Picos, Alina; Dumitrascu, Dan Lucian

    2014-01-01

    Small intestinal bacterial overgrowth is encountered in bowel disorders, including irritable bowel symptoms. Low degrees of inflammation have been recently reported in the irritable bowel syndrome. We looked for the association between intestinal inflammation and small intestinal bacterial overgrowth in irritable bowel syndrome. Small intestinal bacterial overgrowth was assessed by the H2 glucose breath test in 90 consecutive patients with irritable bowel syndrome. A check-up of the oral cavity was carried out before the breath testing. Further on, the patients were classified into two groups, positive and negative, at the breath test. Then they were tested for intestinal inflammation with a fecal test for calprotectin. We used a semiquantitative test for this study. Both groups were compared for the association of intestinal inflammation with small intestinal bacterial overgrowth. A number of 24/90 (26.7%) patients with irritable bowel syndrome had small intestinal bacterial overgrowth. A positive test for intestinal inflammation was significantly more frequent in patients with irritable bowel syndrome and small intestinal bacterial overgrowth (chi(2): p<0.05). Small intestinal bacterial overgrowth is present in almost one quarter of patients with irritable bowel syndrome. It is significantly associated with intestinal inflammation.

  7. Segmental overgrowth syndrome due to an activating PIK3CA mutation identified in affected muscle tissue by exome sequencing

    DEFF Research Database (Denmark)

    Rasmussen, Maria; Sunde, Lone; Weigert, Karen Petra

    2014-01-01

    Mosaic PIK3CA-mutations have been described in an increasing number of overgrowth syndromes. We describe a patient with a previously unreported segmental overgrowth syndrome with the mutation, PIKCA3 c.3140A>G (p.His1047Arg) in affected tissue diagnosed by exome sequencing. This PIK3CA-associated......-associated segmental overgrowth syndrome overlaps with CLOVES syndrome and fibroadipose hyperplasia but is distinct from each of these entities....

  8. Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient Derived iPS Cells

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0414 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient-Derived iPS...3. DATES COVERED 15 Sep 2013 - 14 Sep 2015 4. TITLE AND SUBTITLE Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From... autism pathogenesis: early brain overgrowth and synaptogenesis defects. The goal of this project is to produce human cellular models of non

  9. Differential Diagnoses of Overgrowth Syndromes: The Most Important Clinical and Radiological Disease Manifestations

    Directory of Open Access Journals (Sweden)

    Letícia da Silva Lacerda

    2014-01-01

    Full Text Available Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Some of these syndromes may be associated with dysfunction in the receptor tyrosine kinase (RTK/PI3K/AKT pathway, which results in an increased expression of the insulin receptor. In the current review, four overgrowth syndromes were characterized (Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Madelung’s disease, and neurofibromatosis type I and illustrated using cases from our institution. Because these syndromes have overlapping clinical manifestations and have no established genetic tests for their diagnosis, radiological methods are important contributors to the diagnosis of many of these syndromes. The correlation of genetic discoveries and molecular pathways that may contribute to the phenotypic expression is also of interest, as this may lead to potential therapeutic interventions.

  10. GENERAL OVERGROWTH IN THE FRAGILE-X SYNDROME - VARIABILITY IN THE PHENOTYPIC-EXPRESSION OF THE FMR1 GENE MUTATION

    NARCIS (Netherlands)

    DEVRIES, BBA; ROBINSON, H; STOLTEDIJKSTRA, [No Value; GI, CVTP; DIJKSTRA, PF; VANDOOM, J; HALLEY, DJJ; OOSTRA, BA; TURNER, G; NIERMEIJER, MF

    1995-01-01

    The fragile X syndrome, which often presents in childhood with overgrowth, may in some cases show some diagnostic overlap with classical Sotos syndrome. We describe four fragile X patients with general overgrowth, all of whom are from families with other affected relatives who show the classic

  11. Macrosomia, obesity, macrocephaly and ocular abnormalities (MOMO syndrome) in two unrelated patients: delineation of a newly recognized overgrowth syndrome.

    Science.gov (United States)

    Moretti-Ferreira, D; Koiffmann, C P; Listik, M; Setian, N; Wajntal, A

    1993-06-15

    We describe 2 unrelated patients, a boy and a girl, with an overgrowth syndrome and the following common characteristics: macrocrania, obesity, ocular abnormalities (retinal coloboma and nystagmus), downward slant of palpebral fissures, mental retardation, and delayed bone maturation. Both cases are of sporadic occurrence with no consanguinity between the parents. We suggest that this syndrome is due to a new autosomal dominant mutation and propose to designate it with the acronym of "MOMO syndrome" (Macrosomia, Obesity, Macrocrania, Ocular anomalities.

  12. Polyhydramnios, fetal overgrowth, and macrocephaly: prenatal ultrasound findings of Costello syndrome.

    Science.gov (United States)

    Smith, Laura P; Podraza, John; Proud, Virginia K

    2009-02-15

    Costello syndrome is a multiple congenital anomaly syndrome consisting of dysmorphic facies, cutis laxa, short stature, developmental delay, and mental retardation. Complications include failure to thrive, hypertrophic cardiomyopathy with arrhythmias, and benign and malignant tumors. This report describes a new case of Costello syndrome in a preterm infant born at 27 weeks gestation and diagnosed with Costello syndrome at 7 weeks of life who died at 6 months of age due to cardiac and pulmonary complications. In addition, data were compiled from parent surveys including growth parameters on 16 infants who were subsequently diagnosed with Costello syndrome and had mutation confirmation. The most common prenatal findings in the literature and in this cohort were polyhydramnios and fetal overgrowth with relative macrocephaly. Based on this study, ultrasound identification of polyhydramnios in the context of prenatal overgrowth, especially with relative macrocephaly, needs to raise the possibility of a diagnosis of Costello syndrome in the fetus because of the life-threatening cardiac complications that may occur early in the newborn period.

  13. Chromosome 15q overgrowth syndrome: Prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15(q26.2q26.3

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2011-09-01

    Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.

  14. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  15. Microscopic colitis and small intestinal bacterial overgrowth--diagnosis behind the irritable bowel syndrome?

    Science.gov (United States)

    Stoicescu, Adriana; Andrei, M; Becheanu, G; Stoicescu, M; Nicolaie, T; Diculescu, M

    2012-01-01

    Some patients previously diagnosed with irritable bowel syndrome (IBS) may develop microscopic colitis or small intestinal bacterial overgrowth (SIBO). To estimate the prevalence of microscopic colitis and SIBO in patients with IBS, to evaluate the symptoms and the efficacy of treatment. We examined patients with IBS admitted in our clinic during a three-year period. We identified patients with microscopic colitis by performing total colonoscopy with multiple biopsies from normal intestinal mucosa and those with SIBO by performing a H2-breath test with glucose. We compared the symptoms and the effectiveness of the treatment. Out of the 132 patients initially diagnosed with IBS 3% (n=4) had microscopic colitis and 43.9% (n=58) had SIBO. Diarrhea was the main symptom in patients with microscopic colitis and SIBO (p=0.041), while abdominal pain, abdominal bloating and flatulence were prominent in IBS patients (p=0.042; p=0.039; p=0.048). Specific treatment with rifaximin in SIBO patients negativated H2-breath test in 70.9% cases. Patients suspected to have irritable bowel syndrome should be evaluated for microscopic colitis and SIBO. The proper diagnosis and the specific treatment may cure some difficult cases of the so called "irritable bowel syndrome".

  16. Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool

    Directory of Open Access Journals (Sweden)

    Ksenija Zega

    2017-11-01

    Full Text Available Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically inactivating in mice dual-specificity phosphatase 16 (Dusp16, which is known to negatively regulate mitogen-activated protein kinases (MAPKs and which has never previously been implicated in brain development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16−/− developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct in Dusp16−/− mutants was obstructed during mid-gestation by an expansion of neural progenitors, and during later gestational stages by neurons resulting in a blockage of cerebrospinal fluid (CSF outflow. In contrast, the roof plate and ependymal cells developed normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16−/− mutants as a cause of progenitor overproliferation during mid-gestation. At later gestational stages, this expanded neural progenitor pool generated an increased number of neurons associated with enlarged brain volume. Taken together, we found that Dusp16 plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus.

  17. Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: Experience with Rifaximin

    Science.gov (United States)

    Peralta, Sergio; Cottone, Claudia; Doveri, Tiziana; Almasio, Piero Luigi; Craxi, Antonio

    2009-01-01

    AIM: To estimate the prevalence of small intestinal bacterial overgrowth (SIBO) in our geographical area (Western Sicily, Italy) by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO. METHODS: Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome (IBS); a total of 97 patients accepted to perform a breath test with lactulose (BTLact), and those who had a positive test, received Rifaximin (Normix®, Alfa Wassermann) 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated. RESULTS: Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. CONCLUSION: SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a “breath test”. Rifaximin may represent a valid approach to the treatment of SIBO. PMID:19496193

  18. Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability

    DEFF Research Database (Denmark)

    Tatton-Brown, Katrina; Seal, Sheila; Ruark, Elise

    2014-01-01

    Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband...... and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing...

  19. Brain Fag Syndrome

    African Journals Online (AJOL)

    Introduction. The Brain Fag Syndrome (BFS) was defined in the Diagnostic and. Statistical Manual of Mental Disorders (DSM-IV) as a culture bound syndrome in 1994, just like Koro syndrome and other culture related syndromes.1 BFS is a tetrad of somatic complaints; cognitive impairments; sleep related complaints; and ...

  20. Arteriovenous and lymphatic malformations, linear verrucous epidermal nevus and mild overgrowth: another hamartoneoplastic syndrome?

    NARCIS (Netherlands)

    Hennekam, R. C.; Kwa, V. I.; van Amerongen, A.

    1999-01-01

    We report a 22 year old female presenting with slowly progressive paraparesis, who appeared to have many (mainly subcutaneous) hamartomas. The neurological symptoms were caused by intraspinal masses and arteriovenous malformations. In addition, she had mild overgrowth of one leg and lymph vessel

  1. Somatic PIK3CA mutations in seven patients with PIK3CA-related overgrowth spectrum.

    Science.gov (United States)

    Yeung, Kit San; Ip, Janice Jing Kun; Chow, Chin Pang; Kuong, Evelyn Yue Ling; Tam, Paul Kwong-Hang; Chan, Godfrey Chi-Fung; Chung, Brian Hon-Yin

    2017-04-01

    Somatic mutations in PIK3CA cause many overgrowth syndromes that have been recently coined the "PIK3CA-Related Overgrowth Spectrum." Here, we present seven molecularly confirmed patients with PIK3CA-Related Overgrowth Spectrum, including patients with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome, Klippel-Trenaunay syndrome, lymphatic malformation and two with atypical phenotypes that cannot be classified into existing disease categories. The literature on PIK3CA-Related Overgrowth Spectrum, suggests that PIK3CA c.1258T>C; p.(Cys420Arg), c.1624G>A; p.(Glu542Lys), c.1633G>A; p.(Glu545Lys), c.3140A>G; p.(His1047Arg), and c.3140A>T; p.(His1047Leu) can be identified in approximately 90% of patients without brain overgrowth. Therefore, droplet digital polymerase chain reaction targeting these mutation hotspots could be used as the first-tier genetic test on patients with PIK3CA-Related Overgrowth Spectrum who do not have signs of overgrowth in their central nervous system. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Relationship of periventricular overgrowth to hydrocephalus in brains of fetal rats exposed to benomyl.

    Science.gov (United States)

    Ellis, W G; De Roos, F; Kavlock, R J; Zeman, F J

    1988-01-01

    Benomyl, a benzimidazole fungicide, was administered by gavage to pregnant Sprague-Dawley rats in a daily dose of 62.5 mg/kg of maternal body weight beginning at gestational day (GD) 7. Fetuses examined histologically at GD16 or GD20 revealed a high incidence of craniocerebral anomalies--82.6% of those examined at GD16 and 100% of those examined at GD20. Hydrocephalus occurred in 65.2% of fetuses examined at GD16 and in 58.8% at GD20 but was more severe in the GD20 fetuses. A second common anomaly, termed periventricular "overgrowth" (PVO), consisted of subependymal cell masses that in some fetuses obliterated normal subcortical structures. PVO occurred in 34.8% of fetuses examined at GD16 and 76.5% at GD20. The size of the subependymal masses and the regions involved were considerably greater in the GD20 than the GD16 fetuses. Less common anomalies in the GD20 fetuses were periventricular necrosis (41.2%), a single fetus with exencephaly and another with porencephaly. In the majority of malformed fetuses, the severity of hydrocephalus did not parallel the severity of PVO around the lateral and third ventricles. PVO involved tissues surrounding the cerebral aqueduct in 17.4% of GD16 fetuses and 38.2% of GD20 fetuses. This "overgrowth" distorted the cerebral aqueduct in a large number of fetuses with ventriculomegaly, and at GD20 moderate and severe ventriculomegaly was in every instance associated with a narrow or completely occluded cerebral aqueduct. These relationships suggest that PVO in the midbrain may play a role in the production of aqueductal stenosis and hydrocephalus in this experimental model.

  3. Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

    NARCIS (Netherlands)

    Kalish, J.M.; Doros, L.; Helman, L.J.; Hennekam, R.C.; Kuiper, R.P.; Maas, S.M.; Maher, E.R.; Nichols, K.E.; Plon, S.E.; Porter, C.C.; Rednam, S.; Schultz, K.A.P.; States, L.J.; Tomlinson, G.E.; Zelley, K.; Druley, T.E.

    2017-01-01

    A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America.

  4. Brain Development in Autism: Early Overgrowth Followed by Premature Arrest of Growth

    Science.gov (United States)

    Courchesne, Eric

    2004-01-01

    Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies…

  5. Outbreaks of Acropora white syndrome and Terpios sponge overgrowth combined with coral mortality in Palk Bay, southeast coast of India.

    Science.gov (United States)

    Thinesh, T; Mathews, G; Diraviya Raj, K; Edward, J K P

    2017-09-20

    Acropora white syndrome (AWS) and Terpios sponge overgrowth (TSO) are serious threats to coral communities in various regions; however, information on these 2 lesions in the Indian Ocean is much more limited than in the Indo-Pacific. The present study revealed the impact of these lesions on the Palk Bay reef, India, and covered an area of 7 km2. In total, 1930 colonies were permanently monitored to assess incidences of AWS and TSO and consequent mortality for a period of 1 yr. TSO affected 5 coral genera and caused 20.7% mortality; overall prevalence increased from 1.3% (n = 25) to 25.5% (n = 492). In contrast, AWS only affected Acropora colonies and caused a mortality of 8%; overall prevalence increased from 0.9% (n = 17) to 12.9% (n = 249). Year-round monitoring revealed an increasing trend of both AWS and TSO, followed by temperature rise. These results add to the known geographic distribution of these coral diseases and reveal the impacts of AWS and TSO on coral reefs in the Indian Ocean.

  6. Assessment of 11p loci status of Simpson-Golabi-Behmel (SGBS) somatic overgrowth syndrome and associated embryonal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Xuan, J.Y.; McKenzie, A.E. [Univ. of Ottawa (Canada); Hughes-Benzie, R. [Children`s Hospital of Eastern Ontario (Canada)

    1994-09-01

    SGBS, a somatic overgrowth syndrome which we have recently mapped to Xq25-q27, shows significant clinical overlap with the more common Beckwith-Wiedemann syndrome (BWS) including an increased risk of developing embryonal tumors. Two genes from the BWS-linked 11p15 region, IGF2 and H19, are known to undergo parental imprinting. Relaxation of this imprinting has recently been demonstrated in some BWS cases and isolated Wilm`s tumour (WT). Since SGBS and BWS have been postulated to represent distinct defects in a common pathway, we have studied the methylation pattern and transcriptional activity of IGF2 and H19 in isolated SGBS +/- WT tissue. No consistent methylation abnormalities were observed in genomic DNA isolated from SGBS WBC, placenta, fibroblast or cleft lip tissues. Genotyping of H19 cDNA polymorphisms from SGBS fibroblast revealed normal mono-allelic gene expression. IGF2 is currently being analyzed in a similar fashion. It appears that, in distinction from some cases of BWS, abberant 11p15 loci imprinting is not a factor in SGBS pathogenesis in our study population. Furthermore, genotyping with microsatellites in a large SGBS kindred did not reveal inheritance of a common 11p13-15.5 chromosomal region in the 3 children with WT. Loss of heterozygosity (LOH) secondary to a maternal allele duplication was detected in the 11p15.5 loci in the tumor tissue of both SGBS WTs assayed. Thus, while spontaneous relaxation of 11p15 loci imprinting was not observed in either SGBS or SGBS WT, a de facto LOH-based imprinting abnormality is observed in SGBS associated WT. It is unknown if SGBS predisposes renal cells to LOH or confers a cellular selective advantage following LOH or both.

  7. Capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry and partial/generalized overgrowth (CLAPO): report of six cases of a new syndrome/association.

    Science.gov (United States)

    López-Gutiérrez, Juan Carlos; Lapunzina, Pablo

    2008-10-15

    We report on six patients with clinical findings consisting of (1) Capillary malformation (CM) of the lower lip; (2) Lymphatic malformation (LM) of the face/neck; (3) Asymmetry of face and limbs, and (4) Partial/generalized Overgrowth. This constellation of findings has been observed in six unrelated patients, constituting a likely "new" syndrome/association of capillary-lymphatic-venous malformation and asymmetric overgrowth. 2008 Wiley-Liss, Inc.

  8. brain compartment syndrome

    African Journals Online (AJOL)

    Compartment syndrome of the limbs or the abdomen is a well-known entity in general surgical and orthopaedic practice, characterised by an increase of pressure within a musculofascial compartment leading to progressive neurovascular dysfunction. Although it has not been described as such, raised pressure within the ...

  9. Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity.

    Science.gov (United States)

    Courchesne, Eric; Pierce, Karen

    2005-01-01

    While abnormalities in head circumference in autism have been observed for decades, it is only recently that scientists have begun to focus in on the developmental origins of such a phenomenon. In this article we review past and present literature on abnormalities in head circumference, as well as recent developmental MRI studies of brain growth in this disorder. We hypothesize that brain growth abnormalities are greatest in frontal lobes, particularly affecting large neurons such as pyramidal cells, and speculate how this abnormality might affect neurofunctional circuitry in autism. The relationship to clinical characteristics and other disorders of macrencephaly are discussed.

  10. ABOUT POSSIBLE MECHANISMS OF INTESTINAL BACTERIAL OVERGROWTH IN CHOLELITHIASIS

    Directory of Open Access Journals (Sweden)

    Ya. M. Vakhrushev

    2017-01-01

    Full Text Available The aim. To study the frequency and possible causes of the bacterial overgrowth syndrome in patients with cholelithiasis. Materials and methods. The study involved 76 patients with cholelithiasis. Used the results of endoscopic and radiologic studies in addition to general clinical data. The bacterial overgrowth syndrome determined using the hydrogen breath test with lactulose on LaktofaN2 coater AMA (St. Petersburg. Colonic microflora was assessed by seeding feces on different selective media. Results. In 86,8% of patients with cholelithiasis identified the bacterial overgrowth syndrome, accompanied by numerous clinical manifestations, such as bloating, diarrhea, pain and discomfort in the right iliac region, general weakness and fatigue, loss of weight. In most cases (73,6% patients the bacterial overgrowth syndrome arose against the background of failure ileocecal closing apparatus (75% of patients with prestone stage of cholelithiasis and 82,1% of patients with stone stages of cholelithiasis. In 94,7% of patients had colonic dysbiosis, which promotes cecoileal reflux, thus causing the development of the bacterial overgrowth syndrome. Scarce dysbiosis (decrease of Bifidobacteria, Lactic acid bacteria, Escherichia coli was more pronounced in patients with stage II and III of cholelithiasis, pathogenic dysbiosis (the presence of opportunistic pathogens — in patients with stage I of cholelithiasis. In 55,3% of cases the bacterial overgrowth syndrome was due to both ileocecal failure and impaired colonic microflora. In 26,4% of patients the bacterial overgrowth was stored function of the ileocecal valve. Conclusion. In most cases development of the bacterial overgrowth syndrome is due to the insufficiency of the ileocecal obturator apparatus and colonic dysbiosis.

  11. Abnormal brain synchrony in Down Syndrome.

    Science.gov (United States)

    Anderson, Jeffrey S; Nielsen, Jared A; Ferguson, Michael A; Burback, Melissa C; Cox, Elizabeth T; Dai, Li; Gerig, Guido; Edgin, Jamie O; Korenberg, Julie R

    2013-01-01

    Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks.

  12. Prostatic Inflammation is Determinant for Prostate Overgrowth and Luts Severity in Men with Metabolic Syndrome: Highlights from Two Recently Published Multicentre Studies

    Directory of Open Access Journals (Sweden)

    Mauro Gacci

    2013-12-01

    Full Text Available Introduction: Several evidences have pointed out the possible association between Metabolic Syndrome (MetS and low urinary tract symptoms (LUTS/benign prostate hyperplasia (BPH. Recent epidemiological and histopatological evidences suggested chronic inflammation is a crucial event in BPH pathogenesis. Aim of this study is to demonstrate the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens of patients with BPH, highlighting the results of two recently published multicentre studies analyzing all the data from a preclinical and clinical point of view. Materials and methods: We conducted two retrospective study in 271 and 244 consecutive men treated with simple prostatectomy for LUTS/BPH in two tertiary referral centres. Prostate diameters and volume were measured by transrectal ultrasound, LUTS were scored by IPSS, and obstruction diagnosed by uroflowmetry. MetS was defined according to DF & AHA/NHLBI criteria. The inflammatory infiltrate was investigated according to the scoring system of chronic prostatitis (CP-CPPS and scored as inflammation score (IS ranging 3 to 9 and glandular disruption (GD. In addition, we investigated the in vitro inflammatory effects of metabolic insults on human prostatic myofibroblast cells isolated from BPH patients (hBPH. Results: Of 271 men, 86 (31.7% were affected by MetS. Prostatic volume and the anterior-posterior (AP diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum HDL levels was significantly associated with an increased risk of having a prostatic volume >60cm3. IS in prostatectomy specimens showed a step- wise association with number of MetS factors (p=0.001. Dyslipidaemia was the only factor significantly associated with IS. Positive significant correlations among MetS, IS, GD and IPSS Scores were observed. In myofibroblastic h

  13. CAPGRAS SYNDROME AND ORGANIC BRAIN DYSFUNCTION

    OpenAIRE

    Bhatia, M.S.; Agrwal, Pradeep; Malik, S.C.

    1996-01-01

    Capgras Syndrome was described in the late nineteenth century but its exact pathogenesis is still a source of controversy. Some believe its origin is due to psychodynamic factors whereas others have found the evidence of a generalized or localized brain lesion. We report three cases of Capgras Syndrome occurring in association with frontal lobe lesion.

  14. CAPGRAS SYNDROME AND ORGANIC BRAIN DYSFUNCTION

    Science.gov (United States)

    Bhatia, M.S.; Agrwal, Pradeep; Malik, S.C.

    1996-01-01

    Capgras Syndrome was described in the late nineteenth century but its exact pathogenesis is still a source of controversy. Some believe its origin is due to psychodynamic factors whereas others have found the evidence of a generalized or localized brain lesion. We report three cases of Capgras Syndrome occurring in association with frontal lobe lesion. PMID:21584123

  15. Deep brain stimulation for Tourette syndrome.

    Science.gov (United States)

    Kim, Won; Pouratian, Nader

    2014-01-01

    Gilles de la Tourette syndrome is a movement disorder characterized by repetitive stereotyped motor and phonic movements with varying degrees of psychiatric comorbidity. Deep brain stimulation (DBS) has emerged as a novel therapeutic intervention for patients with refractory Tourette syndrome. Since 1999, more than 100 patients have undergone DBS at various targets within the corticostriatothalamocortical network thought to be implicated in the underlying pathophysiology of Tourette syndrome. Future multicenter clinical trials and the use of a centralized online database to compare the results are necessary to determine the efficacy of DBS for Tourette syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Brain imaging in fibromyalgia syndrome

    National Research Council Canada - National Science Library

    Staud, R

    2011-01-01

    Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome which is characterised by clinical pain as well as widespread hyperalgesia/allodynia to mechanical, thermal, electrical, and chemical stimuli...

  17. Epitaxial Lateral Overgrowth of Semiconductors

    Science.gov (United States)

    Zytkiewicz, Zbigniew R.

    The state of the art and recent developments of lateral overgrowth of compound semiconductors are reviewed. First we focus on the mechanism of epitaxial lateral overgrowth (ELO) from the liquid phase, highlighting the phenomena that are crucial for growing high-quality layers with large aspect ratio. Epitaxy from the liquid phase has been chosen since the equilibrium growth techniques such as liquid-phase epitaxy (LPE) are the most suitable for lateral overgrowth. We then present numerous examples for which the defect filtration in the ELO procedure is very efficient and leads to significant progress in the development of high-performance semiconductor devices made of lattice-mismatched structures. Structural perfection of seams that appear when layers grown from neighboring seeds merge is also discussed. Next, we concentrate on strain commonly found in various ELO structures and arising due to the interaction of ELO layers with the mask. Its origin, and possible ways of its control, are presented. Then we show that the thermal strain in lattice-mismatched ELO structures can be relaxed by additional tilting of ELO wings while still preserving their high quality. Finally, recent progresses in the lateral overgrowth of semiconductors, including new mask materials and liquid-phase electroepitaxial growth on substrates coated by electrically conductive masks, are presented. New versions of the ELO technique from solution and from the vapor (growth from ridges and pendeo-epitaxy) are described and compared with standard ELO. A wide range of semiconductors, including III-V compounds grown from solution and vapor-grown GaN, are used to illustrate phenomena discussed. Very often, the similar behavior of various ELO structures reveals that the phenomena presented are not related to a specific group of compounds or their growth techniques, but have a much more general nature.

  18. Down syndrome: the brain in trisomic mode.

    Science.gov (United States)

    Dierssen, Mara

    2012-12-01

    Down syndrome is the most common form of intellectual disability and results from one of the most complex genetic perturbations that is compatible with survival, trisomy 21. The study of brain dysfunction in this disorder has largely been based on a gene discovery approach, but we are now moving into an era of functional genome exploration, in which the effects of individual genes are being studied alongside the effects of deregulated non-coding genetic elements and epigenetic influences. Also, new data from functional neuroimaging studies are challenging our views of the cognitive phenotypes associated with Down syndrome and their pathophysiological correlates. These advances hold promise for the development of treatments for intellectual disability.

  19. Early brain vulnerability in Wolfram syndrome.

    Directory of Open Access Journals (Sweden)

    Tamara Hershey

    Full Text Available Wolfram Syndrome (WFS is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development.

  20. Brain vascular changes in Cockayne syndrome.

    Science.gov (United States)

    Hayashi, Masaharu; Miwa-Saito, Naho; Tanuma, Naoyuki; Kubota, Masaya

    2012-04-01

    Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are caused by deficient nucleotide excision repair. CS is characterized by cachectic dwarfism, mental disability, microcephaly and progeria features. Neuropathological examination of CS patients reveals dysmyelination and basal ganglia calcification. In addition, arteriosclerosis in the brain and subdural hemorrhage have been reported in a few CS cases. Herein, we performed elastica van Gieson (EVG) staining and immunohistochemistry for collagen type IV, CD34 and aquaporin 4 to evaluate the brain vessels in autopsy cases of CS, XP group A (XP-A) and controls. Small arteries without arteriosclerosis in the subarachnoid space had increased in CS cases but not in either XP-A cases or controls. In addition, string vessels (twisted capillaries) in the cerebral white matter and increased density of CD34-immunoreactive vessels were observed in CS cases. Immunohistochemistry findings for aquaporin 4 indicated no pathological changes in either CS or XP-A cases. Hence, the increased subarachnoid artery space may have caused subdural hemorrhage. Since such vascular changes were not observed in XP-A cases, the increased density of vessels in CS cases was not caused by brain atrophy. Hence, brain vascular changes may be involved in neurological disturbances in CS. © 2011 Japanese Society of Neuropathology.

  1. A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome

    NARCIS (Netherlands)

    Lindhurst, Marjorie J.; Sapp, Julie C.; Teer, Jamie K.; Johnston, Jennifer J.; Finn, Erin M.; Peters, Kathryn; Turner, Joyce; Cannons, Jennifer L.; Bick, David; Blakemore, Laurel; Blumhorst, Catherine; Brockmann, Knut; Calder, Peter; Cherman, Natasha; Deardorff, Matthew A.; Everman, David B.; Golas, Gretchen; Greenstein, Robert M.; Kato, B. Maya; Keppler-Noreuil, Kim M.; Kuznetsov, Sergei A.; Miyamoto, Richard T.; Newman, Kurt; Ng, David; O'Brien, Kevin; Rothenberg, Steven; Schwartzentruber, Douglas J.; Singhal, Virender; Tirabosco, Roberto; Upton, Joseph; Wientroub, Shlomo; Zackai, Elaine H.; Hoag, Kimberly; Whitewood-Neal, Tracey; Robey, Pamela G.; Schwartzberg, Pamela L.; Darling, Thomas N.; Tosi, Laura L.; Mullikin, James C.; Biesecker, Leslie G.

    2011-01-01

    BACKGROUND The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS We performed exome sequencing of DNA from

  2. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  3. Brain stem hypoplasia associated with Cri-du-Chat syndrome.

    Science.gov (United States)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  4. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  5. Brain Stem Hypoplasia Associated with Cri-du-Chat Syndrome

    OpenAIRE

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for th...

  6. Deep brain stimulation for Tourette syndrome.

    Science.gov (United States)

    Visser-Vandewalle, V; Kuhn, J

    2013-01-01

    Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, often associated with behavioral disorders, with typical onset in early childhood. In most patients, the symptoms decrease spontaneously when adulthood is reached, or can be treated with behavioral therapy or medication. Only a small proportion of patients are candidates for surgical treatment. In 1999, thalamic deep brain stimulation (DBS) was introduced for intractable Tourette syndrome. Since then, a diversity of targets have been used, located mainly at the level of the medial part of the thalamus, in the globus pallidus internus (anteromedial limbic and posteroventrolateral motor part), the globus pallidus externus, and the internal capsule/nucleus accumbens. The pathophysiology of Tourette syndrome is still a matter of considerable debate. Current knowledge of cortical-basal ganglia-thalamocortical circuits provides explanations for the beneficial effects of DBS on tics. Inclusion and exclusion criteria have been formulated to identify good candidates for DBS. Because of the small number of patients, there is a strong need for multicenter double-blind trials with standard protocols. © 2013 Elsevier B.V. All rights reserved.

  7. WIEDEMANN SYNDROME

    African Journals Online (AJOL)

    hi-tech

    BILATERAL BENIGN HAEMORRHAGIC ADRENAL CYSTS IN BECKWITH - WIEDEMANN. SYNDROME: CASE REPORT. P. ANOOP and M. A. ANJAY. SUMMARY. Beckwith-Wiedemann syndrome is the most common overgrowth malformation syndrome. The classical features include macrosomia, macroglossia, ...

  8. Brain fag syndrome: a culture-bound syndrome that may be approaching extinction.

    Science.gov (United States)

    Ayonrinde, Oyedeji A; Obuaya, Chiedu; Adeyemi, Solomon Olusola

    2015-08-01

    Aims and method To explore the current salience of 'brain fag' as a nosological, diagnostic and clinical construct in modern West African psychiatry. A semi-structured questionnaire and vignette based on classical symptoms of brain fag syndrome were used to explore current knowledge, explanatory models and practice among Nigerian psychiatrists. Results Of 102 psychiatrists who responded, 98% recognised the term 'brain fag syndrome' and most recognised the scenario presented. However, only 22% made a diagnosis of brain fag syndrome in their practice preferring diagnoses of anxiety, affective and somatic disorders. Clinical implications A decreasing number of Nigerian psychiatrists are making a diagnosis of 'brain fag syndrome'. We found strong evidence of nosological and diagnostic decline in the syndrome in its place of birth. This may signal the early extinction of this disorder or nosological metamorphosis from a 'culture-bound' syndrome in West African psychiatric practice.

  9. Brain structure in pediatric Tourette syndrome.

    Science.gov (United States)

    Greene, D J; Williams Iii, A C; Koller, J M; Schlaggar, B L; Black, K J

    2017-07-01

    Previous studies of brain structure in Tourette syndrome (TS) have produced mixed results, and most had modest sample sizes. In the present multicenter study, we used structural magnetic resonance imaging (MRI) to compare 103 children and adolescents with TS to a well-matched group of 103 children without tics. We applied voxel-based morphometry methods to test gray matter (GM) and white matter (WM) volume differences between diagnostic groups, accounting for MRI scanner and sequence, age, sex and total GM+WM volume. The TS group demonstrated lower WM volume bilaterally in orbital and medial prefrontal cortex, and greater GM volume in posterior thalamus, hypothalamus and midbrain. These results demonstrate evidence for abnormal brain structure in children and youth with TS, consistent with and extending previous findings, and they point to new target regions and avenues of study in TS. For example, as orbital cortex is reciprocally connected with hypothalamus, structural abnormalities in these regions may relate to abnormal decision making, reinforcement learning or somatic processing in TS.

  10. Intranasal Inhalations of Bioactive Factors Produced by M2 Macrophages in Patients With Organic Brain Syndrome

    Science.gov (United States)

    2017-11-06

    Organic Brain Syndrome, Nonpsychotic; Neurocognitive Disorders; Mental Disorder, Organic; Delirium, Dementia, Amnestic, Cognitive Disorders; Nonpsychotic Organic Brain Syndrome; Organic Mental Disorder; Encephalopathy, Post-Traumatic, Chronic; Encephalopathy, Ischemic; Brain Ischemia

  11. Stimulant: A correlate of brain fag syndrome among undergraduate ...

    African Journals Online (AJOL)

    Context: Brain fag syndrome (BFS) is a culture.bound syndrome that occurs commonly among African people involve in intellectual activities like students. The features include intellectual (cognitive) impairment, somatic symptoms, disturbances of affect, and sleepiness. The Psychophysiological Theory identifies the use of ...

  12. Brain FDG-PET Scan and Brain Perfusion SPECT in the Diagnosis of Neuroacanthocytosis Syndromes

    Directory of Open Access Journals (Sweden)

    Eylem Değirmenci

    2015-06-01

    Full Text Available Neuroacanthocytosis syndromes (NA include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. Fluor 18 -2-fluoro-2-deoxyglucose (18F-FDG-PET positron emission tomography (PET and technetium 99m -d, l-hexamethyl-propylene amine oxime (99mTc-HMPAO brain single photon emission computed tomography (SPECT have been increasingly used for the detection of neurologic disorders, such as dementia, epilepsy, and movement disorders. In this case report, we report two patients with neuroacanthocytosis syndromes with the imaging features of brain metabolism by PET and brain perfusion by SPECT. Brain PET and brain SPECT findings of patients with neuroacanthocytosis syndromes were also reviewed.

  13. Phenytoin- and amlodipine-induced gingival overgrowth

    Directory of Open Access Journals (Sweden)

    Ching-Wen Chang

    2012-03-01

    Full Text Available Drug-induced gingival overgrowth is an adverse event associated with three types of drugs, i.e., anticonvulsants, immunosuppressants, and calcium-channel blockers. It was shown that the combined use of an immunosuppressant (cyclosporine and a calcium-channel blocker increases the prevalence and severity of gingival overgrowth. However, few reports discussed the effects of the combination of an anticonvulsant (phenytoin and a calcium-channel blocker (amlodipine. In this case report, we present an epilepsy patient who was using both phenytoin and amlodipine, which caused extensive gingival overgrowth. After periodontal treatment and a gingivectomy, the gingival overgrowth was significantly reduced. A postoperative drug-substitution regimen and intensive professional care ensured a stable result 1 year after surgery.

  14. Chediak-Higashi syndrome: brain MRI and MR spectroscopy manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Lolli, Valentina; Soto Ares, Gustavo; Pruvo, Jean-Pierre [Roger Salengro Hospital, CHRU, Neuroradiology Department, Lille (France); Abou Chahla, Wadih [Jeanne de Flandre Hospital, Pediatric Hematology and Oncology Department, Lille (France); Jissendi-Tchofo, Patrice [University Hospital Saint-Pierre, Radiology Department - Pediatric Neuroradiology Section, Brussels (Belgium)

    2015-08-15

    Chediak-Higashi syndrome is a rare inherited metabolic disorder characterized by partial oculocutaneous albinism, immunodeficiency, and neurological dysfunction. We present the brain magnetic resonance imaging (MRI) and MR spectroscopy (MRS) findings obtained during the accelerated phase of the disorder in an 8-year-old. The brain MRI manifestations at recurrences 15 months and 24 months later are reported as well. (orig.)

  15. Proteus syndrome

    Directory of Open Access Journals (Sweden)

    Criton S

    1995-01-01

    Full Text Available Proteus syndrome is a hamartomatous disorder characterised by focal overgrowths that can involve any structure of the body. An eleven-year-old girl with Proteus syndrome has been described with clitoromegaly.

  16. Immature pattern of brain activity in Rett syndrome

    DEFF Research Database (Denmark)

    Nielsen, J B; Friberg, L; Lou, H

    1990-01-01

    Seven girls with Rett syndrome, a progressive degenerative encephalopathy affecting girls, were studied with single photon emission computed tomography and compared with an aged-matched control group of nine normal children. Global cerebral blood flow was significantly lower in Rett syndrome (54 vs...... 69 mL/100 g per minute), and the flows in prefrontal and temporoparietal association regions of the telencephalon were markedly reduced, whereas the primary sensorimotor regions were relatively spared. The flow distribution in Rett syndrome is very similar to the distribution of brain metabolic...... activity in infants of a few months of age. The abnormal regional cerebral blood flow distribution most likely reflects the widespread functional disturbances in the brain of patients with Rett syndrome, whereas computed tomographic and neuropathologic examination only reveal slight changes when compared...

  17. Guillain Barre Syndrome Following Traumatic Brain Injury: A Rare Case

    OpenAIRE

    Kirac Unal; Karaca Umay; Tombak; Gundogdu; Erdem Sultanoglu; Aytul Cakci

    2016-01-01

    Introduction Guillain-Barre syndrome (GBS) is an immune-mediated acute inflammatory disorder of the peripheral nervous system. Infectious agents were usually accused of playing a role in the etiology of GBS. Guillain-Barre syndrome has rarely been reported following subdural and subarachnoid hemorrhage after head trauma. Case Presentation We report on a 63-year-old male patient presenting GBS following Traumatic Brain Injury (TBI)...

  18. Chronic Inflammatory Gingival Overgrowths: Laser Gingivectomy & Gingivoplasty

    Science.gov (United States)

    Shankar, B Shiva; T, Ramadevi; S, Neetha M; Reddy, P Sunil Kumar; Saritha, G; Reddy, J Muralinath

    2013-01-01

    It is quite common to note chronic inflammatory Gingival overgrowths during and/or post orthodontic treatment. Sometimes the overgrowths may even potentially complicate and/or interrupt orthodontic treatment. With the introduction of soft tissue lasers these problems can now be addressed more easily. Amongst many LASERS now available in Dentistry DIODE LASERS seem to be most ideal for orthodontic soft tissue applications. As newer treatments herald into minimally invasive techniques, DIODE LASERS are becoming more promising both in patient satisfaction and dentist satisfaction. How to cite this article: Shankar BS, Ramadevi T, Neetha M S, Reddy P S K, Saritha G, Reddy J M. Chronic Inflammatory Gingival Overgrowths: Laser Gingivectomy & Gingivoplasty. J Int Oral Health 2013; 5(1):83-87. PMID:24155582

  19. CLOVES syndrome.

    Science.gov (United States)

    Bloom, Jacob; Upton, Joseph

    2013-12-01

    A cohort of patients with overgrowth syndromes has been identified with congenital lipomatous overgrowth, dysregulated fat deposits, and mixed vascular malformations. The acronym CLOVES was given on a heuristic basis to stand for congenital lipomatous overgrowth (CLO), vascular malformation (V), epidermal nevi (E), and scoliosis and spinal deformities (S). These patients have upper limb anomalies with variable phenotypes. Although hand anomalies alone cannot make the diagnosis, the foot, truncal, cutaneous and spinal anomalies are particularly diagnostic. CLOVES syndrome has emerged as a distinct clinical entity diagnosed by clinical and radiographic examinations. The overgrowth pattern is now easily distinguished from other overgrowth syndromes. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  20. Tourette's syndrome and deep brain stimulation

    National Research Council Canada - National Science Library

    Houeto, J L; Karachi, C; Mallet, L; Pillon, B; Yelnik, J; Mesnage, V; Welter, M L; Navarro, S; Pelissolo, A; Damier, P; Pidoux, B; Dormont, D; Cornu, P; Agid, Y

    2005-01-01

    In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf...

  1. Factorial validation and reliability analysis of the brain fag syndrome ...

    African Journals Online (AJOL)

    Background: Brain fag is an indigenous psychopathology or culture-bound syndrome formally documented in Nigeria in the 1960's by Raymond Prince. Objective: The need for a factorial examination of the scale to ensure factorial validity and also to examine the reliability of this screening scale. Methods: Two hundred thirty ...

  2. Fetal Alcohol Syndrome and the Developing Socio-Emotional Brain

    Science.gov (United States)

    Niccols, Alison

    2007-01-01

    Fetal alcohol syndrome (FAS) is currently recognized as the most common known cause of mental retardation, affecting from 1 to 7 per 1000 live-born infants. Individuals with FAS suffer from changes in brain structure, cognitive impairments, and behavior problems. Researchers investigating neuropsychological functioning have identified deficits in…

  3. Gingival Overgrowth and Associated Factors among Epileptic ...

    African Journals Online (AJOL)

    Bio-data and medical history were collected using a structured self-administered questionnaire and confirmed from patients' case file. Oral hygiene was assessed using the Simplified Oral Hygiene Index (S-OHI) of Green and Vermillion and GO, the New Clinical Index for Drug-Induced Gingival Overgrowth (DIGO). Result: ...

  4. The metabolic syndrome: a brain disease?

    NARCIS (Netherlands)

    Buijs, R.M.; Kreier, F.

    2006-01-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each

  5. Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration

    National Research Council Canada - National Science Library

    Wendy Morley; Stephanie Seneff

    2014-01-01

    .... Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading...

  6. Brain in complex regional pain syndrome

    OpenAIRE

    Hotta, Jaakko

    2017-01-01

    Complex regional pain syndrome (CRPS) causes disabling and severe limb pain that is difficult to treat. The pain typically increases during motor actions, but is present also at rest. The pathophysiology of CRPS is incompletely understood. Some of the symptoms suggest involvement of the central nervous system, and accordingly, patients have been shown to display alterations in, for instance, the primary sensorimotor cortex (SM1) and indications of neuroinflammation. More thorough pathophysiol...

  7. [Intracranial hypertension in Proteus syndrome].

    Science.gov (United States)

    Dandine, J-B; James, S; Van Garsse, A; Born, J-D

    2007-11-01

    Proteus syndrome, described for the first time in 1979, is a sporadic congenital poly-malformation syndrome named for its highly variable manifestations. We report the case of a 36-year-old male patient with several malformations including skull hyperostosis and huge frontal sinus hypertrophy compressing the brain. He complained of increasing headache for 5 years. Cerebrospinal fluid pressure monitoring revealed severe hypertension. The patient underwent frontoparietal craniectomy, which allowed partial decompression. Postoperatively headaches decreased and the intracranial pressure normalized. Proteus syndrome is a genetic disease with a mosaic pattern. Only a hundred cases have been reported, mostly in childhood. Common manifestations include disproportionate overgrowth of the limbs and the skull, various subcutaneous tumors, vascular, renal and pulmonary malformations. Brain abnormalities are not common in this syndrome. When present, retardation or seizure disorders are typically seen. Intracranial hypertension is described for the first time in this syndrome.

  8. Irritable bowel syndrome, the microbiota and the gut-brain axis

    DEFF Research Database (Denmark)

    Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

    2016-01-01

    nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review...... recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome....

  9. The Use of Deep Brain Stimulation in Tourette Syndrome

    OpenAIRE

    Ladan Akbarian-Tefaghi; Ludvic Zrinzo; Thomas Foltynie

    2016-01-01

    Tourette syndrome (TS) is a childhood neurobehavioural disorder, characterised by the presence of motor and vocal tics, typically starting in childhood but persisting in around 20% of patients into adulthood. In those patients who do not respond to pharmacological or behavioural therapy, deep brain stimulation (DBS) may be a suitable option for potential symptom improvement. This manuscript attempts to summarise the outcomes of DBS at different targets, explore the possible mechanisms of acti...

  10. Editorial: Brain Fag Syndrome: New Wine in Old Bottles or Old Wine ...

    African Journals Online (AJOL)

    Brain Fag Syndrome has been described as a culture bound syndrome associated with mental exertion and study in West Africans. Modern psychiatric and social science literature over the last half century describe the emanation of the term “brain fag” as well as the syndrome in Nigeria. Characterised by somatic, affective, ...

  11. High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice

    OpenAIRE

    Jones, Helen N.; Woollett, Laura A.; Barbour, Nicolette; Prasad, Puttur D.; Powell, Theresa L.; Jansson, Thomas

    2009-01-01

    Maternal overweight and obesity in pregnancy often result in fetal overgrowth, which increases the risk for the baby to develop metabolic syndrome later in life. However, the mechanisms underlying fetal overgrowth are not established. We developed a mouse model and hypothesized that a maternal high-fat (HF) diet causes up-regulation of placental nutrient transport, resulting in fetal overgrowth. C57BL/6J female mice were fed a control (11% energy from fat) or HF (32% energy from fat) diet for...

  12. Brain tumors and anorexia nervosa syndrome.

    Science.gov (United States)

    Chipkevitch, E

    1994-01-01

    This review presents 21 cases, found in the literature, of a CNS lesion (a tumor in 19 of them) associated with emaciation, anorexia and several psychic symptoms that had led to the diagnosis of anorexia nervosa (AN). Anorexia and psychic disturbances preceded the neurologic signs and/or the correct diagnosis in all patients (by a mean of 2.9 years, range = 0.2-17 years). Anorexia had begun before the age of 25 years in 18 patients of which two-thirds were females. Only a few cases fulfilled the DSM-III-R criteria for AN; the majority could be characterized as 'atypical AN'. Although AN is usually conceived as a primarily psychogenic disorder, structural lesions of the hypothalamus (or other sites involved in food regulation) in animal models and in these human cases mimic many features of AN, suggesting the possibility of an as yet unidentified structural hypothalamic disorder to be implicated in the etiopathogeny of AN. The unusually high incidence of germ-cell tumors in this review (33%) suggests that they are more likely than other tumors to influence the limbic system toward an anorectic syndrome.

  13. [Intestinal bacteria overgrowth in chronic hepatopathies].

    Science.gov (United States)

    Casafont, F; Almohalla, C; Garcia Pajares, F; Pons Romero, F

    1998-01-01

    Intestinal bacterial overgrowth (IBD) is very frequent in patients with chronic hepatopathies. Causes of IBO, although not entirely known, principally are: the hepatopathy, the alcoholism and the alterations produced by these two factors, such as achylia (and above all hypochlorhydria), decrease in the secretion of IgA, and malnutrition. On the other hand, the IBO increases the severity of the hepatopathy and frequently produces a bacterial peritonitis. All these data suggest that the IBO play an important role increasing the hepatopathy severity and consequently is a factor to bear in mind.

  14. Deep brain stimulation for the treatment of uncommon tremor syndromes.

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Okun, Michael S

    2016-08-01

    Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. In this article, we conducted a PubMed search using different combinations between the terms 'Uncommon tremors', 'Dystonic tremor', 'Holmes tremor' 'Midbrain tremor', 'Rubral tremor', 'Cerebellar tremor', 'outflow tremor', 'Multiple Sclerosis tremor', 'Post-traumatic tremor', 'Neuropathic tremor', and 'Deep Brain Stimulation/DBS'. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.

  15. Guillain Barre Syndrome Following Traumatic Brain Injury: A Rare Case

    Directory of Open Access Journals (Sweden)

    Kirac Unal

    2016-06-01

    Full Text Available Introduction Guillain-Barre syndrome (GBS is an immune-mediated acute inflammatory disorder of the peripheral nervous system. Infectious agents were usually accused of playing a role in the etiology of GBS. Guillain-Barre syndrome has rarely been reported following subdural and subarachnoid hemorrhage after head trauma. Case Presentation We report on a 63-year-old male patient presenting GBS following Traumatic Brain Injury (TBI. Only five other similar cases are described in the literature. Conclusions Sudden onset of GBS symptoms following trauma may erroneously be assessed as secondary complications of the TBI and can lead to unnecessary procedures such as computerized tomography (CT scan and magnetic resonance imaging (MRI for a definitive diagnosis and may be a waste of time.

  16. Tourette syndrome deep brain stimulation: a review and updated recommendations.

    Science.gov (United States)

    Schrock, Lauren E; Mink, Jonathan W; Woods, Douglas W; Porta, Mauro; Servello, Dominico; Visser-Vandewalle, Veerle; Silburn, Peter A; Foltynie, Thomas; Walker, Harrison C; Shahed-Jimenez, Joohi; Savica, Rodolfo; Klassen, Bryan T; Machado, Andre G; Foote, Kelly D; Zhang, Jian-Guo; Hu, Wei; Ackermans, Linda; Temel, Yasin; Mari, Zoltan; Changizi, Barbara K; Lozano, Andres; Auyeung, M; Kaido, Takanobu; Agid, Yves; Welter, Marie L; Khandhar, Suketu M; Mogilner, Alon Y; Pourfar, Michael H; Walter, Benjamin L; Juncos, Jorge L; Gross, Robert E; Kuhn, Jens; Leckman, James F; Neimat, Joseph A; Okun, Michael S

    2015-04-01

    Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25-year-old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post-DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients. © 2014 International Parkinson and Movement Disorder Society.

  17. The Use of Deep Brain Stimulation in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Ladan Akbarian-Tefaghi

    2016-08-01

    Full Text Available Tourette syndrome (TS is a childhood neurobehavioural disorder, characterised by the presence of motor and vocal tics, typically starting in childhood but persisting in around 20% of patients into adulthood. In those patients who do not respond to pharmacological or behavioural therapy, deep brain stimulation (DBS may be a suitable option for potential symptom improvement. This manuscript attempts to summarise the outcomes of DBS at different targets, explore the possible mechanisms of action of DBS in TS, as well as the potential of adaptive DBS. There will also be a focus on the future challenges faced in designing optimized trials.

  18. The Use of Deep Brain Stimulation in Tourette Syndrome.

    Science.gov (United States)

    Akbarian-Tefaghi, Ladan; Zrinzo, Ludvic; Foltynie, Thomas

    2016-08-19

    Tourette syndrome (TS) is a childhood neurobehavioural disorder, characterised by the presence of motor and vocal tics, typically starting in childhood but persisting in around 20% of patients into adulthood. In those patients who do not respond to pharmacological or behavioural therapy, deep brain stimulation (DBS) may be a suitable option for potential symptom improvement. This manuscript attempts to summarise the outcomes of DBS at different targets, explore the possible mechanisms of action of DBS in TS, as well as the potential of adaptive DBS. There will also be a focus on the future challenges faced in designing optimized trials.

  19. Small Intestinal Bacterial Overgrowth: A Case-Based Review

    Directory of Open Access Journals (Sweden)

    Kristen H. Reynolds

    2015-11-01

    Full Text Available Small intestinal bacterial overgrowth (SIBO is a condition of increased microbial load in the small intestine. The microbes feed on dietary carbohydrates and starches via fermentation, leading to gas production, inflammation and damage to the lining of the small intestine. Clinical presentation is varied, including abdominal pain, bloating, malabsorption and systemic symptoms. SIBO is associated with many challenging and chronic conditions such as fibromyalgia, chronic fatigue and chronic pain syndromes, and has been shown to be a causative factor in two out of three cases of irritable bowel syndrome. Symptoms improve with antimicrobial treatment, but recurrence is common. Many providers may not be aware of SIBO. This narrative review highlights a clinical case and the most recent literature regarding SIBO, including history, clinical presentation, prevalence, pathophysiology, diagnostic workup, treatment and prevention. Integrative medicine approaches, including diet, supplements and manual therapies, are also reviewed. SIBO can be a challenging condition and requires an integrative, patient-centered approach. Further studies are needed to guide clinicians in the workup and treatment of SIBO.

  20. Bacteria: a new player in gastrointestinal motility disorders--infections, bacterial overgrowth, and probiotics.

    LENUS (Irish Health Repository)

    Quigley, Eamonn M M

    2012-02-03

    Irritable bowel syndrome (IBS) may result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa, which in turn leads to immune activation in the colonic mucosa. Some propose that bacterial overgrowth is a common causative factor in the pathogenesis of symptoms in IBS; others point to evidence suggesting that the cause stems from more subtle qualitative changes in the colonic flora. Bacterial overgrowth will probably prove not to be a major factor in what will eventually be defined as IBS. Nevertheless, short-term therapy with either antibiotics or probiotics seems to reduce symptoms among IBS patients. However, in the long term, safety issues will favor the probiotic approach; results of long-term studies with these agents are eagerly awaited.

  1. Oxidative stress induces overgrowth of the Drosophila neuromuscular junction.

    Science.gov (United States)

    Milton, Valerie J; Jarrett, Helen E; Gowers, Kate; Chalak, Salma; Briggs, Laura; Robinson, Iain M; Sweeney, Sean T

    2011-10-18

    Synaptic terminals are known to expand and contract throughout an animal's life. The physiological constraints and demands that regulate appropriate synaptic growth and connectivity are currently poorly understood. In previous work, we identified a Drosophila model of lysosomal storage disease (LSD), spinster (spin), with larval neuromuscular synapse overgrowth. Here we identify a reactive oxygen species (ROS) burden in spin that may be attributable to previously identified lipofuscin deposition and lysosomal dysfunction, a cellular hallmark of LSD. Reducing ROS in spin mutants rescues synaptic overgrowth and electrophysiological deficits. Synapse overgrowth was also observed in mutants defective for protection from ROS and animals subjected to excessive ROS. ROS are known to stimulate JNK and fos signaling. Furthermore, JNK and fos in turn are known potent activators of synapse growth and function. Inhibiting JNK and fos activity in spin rescues synapse overgrowth and electrophysiological deficits. Similarly, inhibiting JNK, fos, and jun activity in animals with excessive oxidative stress rescues the overgrowth phenotype. These data suggest that ROS, via activation of the JNK signaling pathway, are a major regulator of synapse overgrowth. In LSD, increased autophagy contributes to lysosomal storage and, presumably, elevated levels of oxidative stress. In support of this suggestion, we report here that impaired autophagy function reverses synaptic overgrowth in spin. Our data describe a previously unexplored link between oxidative stress and synapse overgrowth via the JNK signaling pathway.

  2. Altered Brain Glucose Consumption in Cogan’s Syndrome

    Directory of Open Access Journals (Sweden)

    Paolo Mora

    2016-01-01

    Full Text Available Purpose. Prospective, controlled cohort study to investigate possible alterations in brain glucose metabolism (CMRglc in patients with Cogan’s syndrome (CS. Patients and Methods. Functional mapping of the CMRglc was obtained by quantitative molecular imaging positron emission tomography, combined with computed tomography (FDG-PET/CT. The patients were divided into three clinical groups: typical CS; atypical CS (ACS; autoimmune inner ear disease (AIED. The unmatched control group (CG consisted of subjects requiring FDG-PET/CT for an extracranial pathology. Statistical mapping searched areas of significant glucose hypometabolism in all the affected patients (DG and in each clinical subgroup. The results were compared with those of the CG. Results. 44 patients were enrolled (DG and assigned to the three study groups: 8 patients to the CS group; 21 patients to the ACS group; and 15 to the AIED group. Sixteen subjects formed the CG group. Areas of significant brain glucose hypometabolism were identified in all the study groups, with the largest number and extension in the DG and CS. Conclusions. This study revealed areas of significantly altered CMRglc in patients with CS (any subform without neurologic complains and normal conventional neuroimaging. Our results suggest that FDG-PET/CT may represent a very useful tool for the global assessment of patients with Cogan’s syndrome.

  3. Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning

    NARCIS (Netherlands)

    Joshi, U.; van der Sluijs, J.A.; Teule, G.J.; Pijpers, R.

    2005-01-01

    Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and

  4. Brain morphology in children with nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Shiohama, Tadashi; Fujii, Katsunori; Miyashita, Toshiyuki; Mizuochi, Hiromi; Uchikawa, Hideki; Shimojo, Naoki

    2017-04-01

    Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS. We evaluated brain T1-weighted images from nine children with NBCCS and 15 age-matched normal control (NC) children (mean [standard deviation], 12.2 [2.8] vs. 11.6 [2.3] years old). The diameters of the cerebrum, corpus callosum, and brain stem and the cerebellar volume were compared using two-tailed t-tests with Welch's correction. The transverse diameters (150.4 [9.9] vs. 136.0 [5.5] mm, P = 0.002) and longitudinal diameters (165.4 [8.0] vs. 151.3 [8.7] mm, P = 0.0007) of the cerebrum, cross-sectional area of the cerebellar vermis (18.7 [2.6] vs. 11.8 [1.7] cm 2 , P = 0.0001), and total volume of the cerebellar hemispheres (185.1 [13.0] vs. 131.9 [10.4] cm 3 , P = 0.0001) were significantly larger in the children with NBCCS than in NC children. Thinning of the corpus callosum and ventricular enlargement were also confirmed in children with NBCCS. We demonstrate that, on examination of the brain morphology, an increase in the size of the cerebrum, cerebellum, and cerebral ventricles is revealed in children with NBCCS compared to NC children. This suggests that constitutively active hedgehog signaling affects human brain morphology and the PI3K/AKT and RAS/MAPK pathways. © 2017 Wiley Periodicals, Inc.

  5. Gut-Brain Axis and Metabolism in Polycystic Ovary Syndrome.

    Science.gov (United States)

    Saydam, Basak Ozgen; Yildiz, Bulent O

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder, often accompanied and complicated by insulin resistance, glucose intolerance and obesity. Gut, brain and metabolism are highly related with each other in obesity and diabetes as well as in PCOS. Central nervous system regulates food intake through complex interactions of homeostatic and hedonic systems while gastrointestinal system contributes to food intake and metabolism via orexigenic and anorexigenic gastrointestinal hormones. Ghrelin is the only circulating orexigenic hormone whereas anorexigenic peptides include glucagon like peptide-1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY) and cholecystokinin (CCK). Compared to healthy women, patients with PCOS show decreased or unaltered fasting ghrelin levels, along with decreased or unaltered postprandial suppression of this hormone. GLP-1, PYY and CCK show unaltered or decreased levels both in fasting and postprandial states in PCOS whereas fasting levels of another gut hormone, GIP is either unaltered or increased. Dietary interventions associated with weight loss or short term oral contraceptive use in PCOS do not alter fasting or postprandial levels of these hormones. However use of metformin is associated with an increase in ghrelin, PYY, GLP-1 and GIP in women with PCOS. GLP-1 agonists and bariatric surgery, both having a significant impact on gut-brain axis, appear to be effective therapeutic options in obese women with PCOS. Finally, alterations in gut microbiota and possible interactions with gut-brain axis in PCOS is a topic of interest. Understanding the relationship between PCOS and homeostatic and hedonic systems, gastrointestinal hormones, and gut microbiota as well as potential effects of different therapeutic interventions on these systems will provide further understanding and novel treatment opportunities for this syndrome.

  6. Early Generalized Overgrowth in Boys With Autism

    Science.gov (United States)

    Chawarska, Katarzyna; Campbell, Daniel; Chen, Lisha; Shic, Frederick; Klin, Ami; Chang, Joseph

    2016-01-01

    Context Multiple studies have reported an overgrowth in head circumference (HC) in the first year of life in autism. However, it is unclear whether this phenomenon is independent of overall body growth and whether it is associated with specific social or cognitive features. Objectives To examine the trajectory of early HC growth in autism compared with control groups; to assess whether HC growth in autism is independent of height and weight growth during infancy; and to examine HC growth from birth to 24 months in relationship to social, verbal, cognitive, and adaptive functioning levels. Design Retrospective study. Setting A specialized university-based clinic. Participants Boys diagnosed as having autistic disorder (n=64), pervasive developmental disorder–not otherwise specified (n=34), global developmental delay (n=13), and other developmental problems (n=18) and typically developing boys (n=55). Main Outcome Measures Age-related changes in HC, height, and weight between birth and age 24 months; measures of social, verbal, and cognitive functioning at age 2 years. Results Compared with typically developing controls, boys with autism were significantly longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by age 11.4 months (P=.05 for all). None of the other clinical groups showed a similar overgrowth pattern. Boys with autism who were in the top 10% of overall physical size in infancy exhibited greater severity of social deficits (P=.009) and lower adaptive functioning (P=.03). Conclusions Boys with autism experienced accelerated HC growth in the first year of life. However, this phenomenon reflected a generalized process affecting other morphologic features, including height and weight. The study highlights the importance of studying factors that influence not only neuronal development but also skeletal growth in autism. PMID:21969460

  7. Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Costa, D.C.; Gacinovic, S.; Miller, R.F. [London University College Medical School, Middlesex Hospital, London (United Kingdom)

    1995-09-01

    Infection with the Human Immunodeficiency Virus type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the Acquired Immunodeficiency Syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin`s B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). It is studied the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion Single Photon Emission Tomography (SPET), neuroreceptor and Positron Emission Tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumour markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with {sup 201}Tl using quantification (tumour to non-tumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.

  8. Twiddler's syndrome in a patient with a deep brain stimulation device for generalized dystonia

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Schweder, Patrick M; Joint, Carole

    2011-01-01

    Deep brain stimulation (DBS) is the technique of neurostimulation of deep brain structures for the treatment of conditions such as essential tremor, dystonia, Parkinson's disease and chronic pain syndromes. The procedure uses implanted deep brain stimulation electrodes connected to extension leads...

  9. Irritable bowel syndrome, the microbiota and the gut-brain axis.

    Science.gov (United States)

    Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian; Rosenberg, Jacob

    2016-09-02

    Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome.

  10. The use of deep brain stimulation in Tourette's syndrome.

    Science.gov (United States)

    Rotsides, Janine; Mammis, Antonios

    2013-11-01

    Tourette's syndrome (TS) is a childhood neuropsychiatric disorder characterized by multiple involuntary motor and vocal tics. It is commonly associated with other behavioral disorders including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, depression, and self-injurious behaviors. Tourette's syndrome can be effectively managed with psychobehavioral and pharmacological treatments, and many patients experience an improvement in tics in adulthood. However, symptoms may persist and cause severe impairment in a small subset of patients despite available therapies. In recent years, deep brain stimulation (DBS) has been shown to be a promising treatment option for such patients. Since the advent of its use in 1999, multiple targets have been identified in DBS for TS, including the medial thalamus, globus pallidus internus, globus pallidus externus, anterior limb of the internal capsule/nucleus accumbens, and subthalamic nucleus. While the medial thalamus is the most commonly reported trajectory, the optimal surgical target for TS is still a topic of much debate. This paper provides a review of the available literature regarding the use of DBS for TS.

  11. Brain Perfusion in Corticobasal Syndrome with Progressive Aphasia

    Directory of Open Access Journals (Sweden)

    Yoshitake Abe

    2016-04-01

    Full Text Available Background: Brain perfusion may differ between patients with corticobasal syndrome (CBS with and without aphasia. Methods: Twenty-six (9 males and 17 females; mean age 76 ± 5.3 years patients with CBS were enrolled in the study. Brain MRI and single-photon emission computed tomography were performed in all subjects. Language was evaluated using the Standard Language Test of Aphasia. The patients were divided into two subgroups according to the presence or absence of progressive aphasia. Differences in the regional cerebral blood flow (rCBF between the two groups were detected based on voxel-by-voxel group analysis using Statistical Parametric Mapping 8. Results: All patients exhibited asymmetric motor symptoms and signs, including limb apraxia, bradykinesia, and akinetic rigidity. Of 26 patients, 9 had a clinically obvious language disturbance, characterized as nonfluent aphasia. Almost all CBS patients with aphasia exhibited cortical atrophy predominantly in the left frontal and temporal lobes with widening of the Sylvian fissure on MRI. The rCBF in the left middle frontal gyrus differed significantly between CBS patients with and without aphasia. Conclusion: CBS patients with aphasia exhibit motor symptoms predominantly on the right side and cortical atrophy mainly in the left perisylvian cortices. In particular, left frontal dysfunction might be related to nonfluent aphasia in CBS.

  12. Irritable bowel syndrome: Is it "irritable brain" or "irritable bowel"?

    Directory of Open Access Journals (Sweden)

    Susanta Kumar Padhy

    2015-01-01

    Full Text Available Irritable bowel syndrome (IBS has been recognized as one of the most common and best studied disorders among the group of functional gastrointestinal disorders. It is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or a change in bowel habit. In the Western world, IBS appears to affect up to 20% of the population at any given time but in Asian countries, the median value of IBS prevalence defined by various criteria ranges between 6.5% and 10.1%, and community prevalence of 4% is found in North India. Those attending gastroenterology clinics represent only the tip of the iceberg. The disorder substantially impairs the quality of life, and the overall health-care costs are high. IBS has therefore gained increased attention from clinicians, researchers, and pharmaceutical industries. It is often frustrating to both patients and physicians as the disease is usually chronic in nature and difficult to treat. However, the understanding of IBS has been changing from time to time and still most of its concepts are unknown. In this review we have discussed, debated, and synthesized the evidence base, focusing on underlying mechanisms in the brain and bowel. We conclude that it is both brain and bowel mechanisms that are responsible. The clinical implication of such mechanisms is discussed.

  13. Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

    Science.gov (United States)

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

  14. PREVALENCE OF SMALL INTESTINE BACTERIAL OVERGROWTH IN PATIENTS WITH GASTROINTESTINAL SYMPTOMS

    Directory of Open Access Journals (Sweden)

    Carolina Piedade MARTINS

    2017-02-01

    Full Text Available ABSTRACT BACKGROUND Small intestine bacterial overgrowth is a heterogeneous syndrome characterized by an increase in the number and/or the presence of atypical microbiota in the small intestine. The symptoms of small intestine bacterial overgrowth are unspecific, encompassing abdominal pain/distension, diarrhea and flatulence. Due to the increased cost and complexity for carrying out the jejunal aspirate, the gold standard for diagnosis of the syndrome, routinely the hydrogen (H 2 breath test has been used, utilizing glucose or lactulose as substrate, which is able to determine, in the exhaled air, the H 2 concentration produced from the intestinal bacterial metabolism. However, due to a number of individuals presenting a methanogenic microbiota, which does not produce H 2 , the testing on devices capable of detecting, concurrently, the concentration of exhaled H 2 and methane (CH 4 is justified. OBJECTIVE This study aimed to determine the prevalence of small intestine bacterial overgrowth in patients with digestive symptoms, through a comparative analysis of breath tests of H 2 or H 2 and CH 4 associated, using glucose as substrate . METHODS A total of 200 patients of both sexes without age limitation were evaluated, being directed to a Breath Test Laboratory for performing the H 2 test (100 patients and of exhaled H 2 and CH 4 (100 patients due to gastrointestinal complaints, most of them patients with gastrointestinal functional disorders. RESULTS The results indicated a significant prevalence of small intestine bacterial overgrowth in the H 2 test and in the test of exhaled H 2 and CH 4 (56% and 64% respectively in patients with gastrointestinal symptoms, and higher prevalence in females. It found further that methane gas was alone responsible for positivity in 18% of patients. CONCLUSION The data found in this study is consistent with the findings of the current literature and underscores the need for using devices capable of capturing the

  15. Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury

    OpenAIRE

    Arnaud Messé; Sophie Caplain; Mélanie Pélégrini-Issac; Sophie Blancho; Richard Lévy; Nozar Aghakhani; Michèle Montreuil; Habib Benali; Stéphane Lehéricy

    2013-01-01

    Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the D...

  16. Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome in traumatic brain injury.

    Science.gov (United States)

    John, Cynthia A; Day, Michael W

    2012-04-01

    Central neurogenic diabetes insipidus, syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome are secondary events that affect patients with traumatic brain injury. All 3 syndromes affect both sodium and water balance; however, they have differences in pathophysiology, diagnosis, and treatment. Differentiating between hypernatremia (central neurogenic diabetes insipidus) and the 2 hyponatremia syndromes (syndrome of inappropriate secretion of antidiuretic hormone, and cerebral salt-wasting syndrome) is critical for preventing worsening neurological outcomes in patients with head injuries.

  17. Primary brain tumors and posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Kamiya-Matsuoka, Carlos; Cachia, David; Olar, Adriana; Armstrong, Terri S; Gilbert, Mark R

    2014-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBTs). The aim of this study was to analyze the clinicoradiological features and report the clinical outcomes of PRES in PBT patients. We identified 4 cases with PBT who developed PRES at MD Anderson Cancer Center (MDACC) between 2012 and 2014. Clinical and radiological data were abstracted from their records. In addition, we also solicited 8 cases from the literature. The median age at PRES onset was 19 years, male-to-female ratio was 1:1, and the syndrome occurred in patients with ependymoma (n = 4), glioblastoma (n = 3), diffuse intrinsic pontine glioma (DIPG; n = 3), juvenile pilocytic astrocytoma (n = 1), and atypical meningioma (n = 1). Two glioblastomas and 2 DIPG cases received bevacizumab and vandetanib before the onset of symptoms, respectively. The most common clinical presentation was seizures (n = 7). Three MDACC patients recovered completely in 3-4 weeks after the onset of symptoms. One patient died due to active cancer and several comorbidities including PRES. Hypertension seems to be the most important coexisting risk factor for development of PRES; however, the potential effects of chemotherapeutic agents in the pathogenesis of PRES should also be examined. The clinicoradiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. PRES must be considered as part of the differential diagnosis in patients with PBTs presenting with seizures or acute encephalopathy.

  18. Epitaxial lateral overgrowth of GaN

    Energy Technology Data Exchange (ETDEWEB)

    Beaumont, B.; Vennegues, P.; Gibart, P. [CNRS, Sophia Antipolis, Valbonne (France). CRHEA

    2001-09-01

    Since there is no GaN bulk single crystal available, the whole technological development of GaN based devices relies on heteroepitaxy. Numerous defects are generated in the heteroepitaxy of GaN on sapphire or 6H-SiC, mainly threading dislocations (TDs). Three types of TDs are currently observed, a type (with Burgers vector 1/3 left angle 11 anti 20 right angle); c type (with left angle 0001 right angle) and mixed a + c (1/3 left angle 11 anti 23 right angle). The epitaxial lateral overgrowth (ELO) technology produces high quality GaN with TD densities in the mid 10{sup 6} cm{sup -2}, linewidth of the low-temperature photoluminescence (PL) near-bandgap recombination peaks <1 meV and deep electron traps reduced below 10{sup 14} cm{sup -3} (compared to mid 10{sup 15} cm{sup -3} in standard GaN). Numerous modifications of the ELO process have been proposed in order either to avoid technological steps (mask-less ELO) or to improve it (pendeo-epitaxy). Basically developed on either sapphire or 6H-SiC, the ELO technology is also achievable on (111)Si or (111)3C-SiC/Si provided that an appropriate buffer layer is grown to avoid cracks. More sophisticated technologies have been implemented to further increase the useable part of the ELO GaN surface (two technological steps, three-step ELO). Unfortunately, in-depth understanding of the basic ELO process is still missing, i.e. of the growth anisotropy and bending of dislocations. (orig.)

  19. Brain Atrophy and Hypomyelination Associated with Iatrogenic Cushing Syndrome in an Infant.

    Science.gov (United States)

    Dogan, Sumeyra; S Dogan, Mehmet; Tutunculer, Filiz; Yapiciugurlar, Ozge; Genchellac, Hakan

    2018-01-01

    Prolonged use of topical corticosteroids, particularly in infants, albeit rare, may lead to Cushing syndrome. Central nervous system abnormalities including brain atrophy and delayed myelination on cranial magnetic resonance imaging has been reported in patients with corticosteroid treatment. We herein report a 5-month-old female infant referred to Department of Pediatric Endocrinology, Edirne, Turkey with brain atrophy and myelination delay that might be due to iatrogenic Cushing syndrome caused by topical corticosteroid use.

  20. Violence: heightened brain attentional network response is selectively muted in Down syndrome.

    Science.gov (United States)

    Anderson, Jeffrey S; Treiman, Scott M; Ferguson, Michael A; Nielsen, Jared A; Edgin, Jamie O; Dai, Li; Gerig, Guido; Korenberg, Julie R

    2015-01-01

    The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated

  1. Genes, Brain Development and Psychiatric Phenotypes in Velo-Cardio-Facial Syndrome

    Science.gov (United States)

    Gothelf, Doron; Schaer, Marie; Eliez, Stephan

    2008-01-01

    Velo-cardio-facial syndrome (VCFS) has been in the focus of intensive research over the last 15 years. The syndrome represents a homogeneous model for studying the effect of a decreased dosage of genes on the development of brain structure and function and, consequently, on the emergence of schizophrenia-like psychotic disorder. In this review, we…

  2. C syndrome in an Egyptian infant with dilated brain ventricles and ...

    African Journals Online (AJOL)

    C syndrome is an autosomal recessive disorder characterized by trigonocephaly, partial or complete obliteration of the metopic suture which is characteristic, and short limbs. In this paper we describe an Egyptian boy affected with this syndrome, with no exophthalmos and with dilated brain ventricles and heterotopia.

  3. Brain Fag Syndrome – a myth or a reality | Ola | African Journal of ...

    African Journals Online (AJOL)

    The Brain Fag Syndrome (BFS) is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culture bound syndrome. BFS is a tetrad of somatic complaints; cognitive impairments; sleep related complaints; and other somatic impairments. Prince first described this psychiatric illness associated with ...

  4. Brain and ventricular volume in patients with syndromic and complex craniosynostosis

    NARCIS (Netherlands)

    T. de Jong (Tim); B.F.M. Rijken (Bianca); M. Leguin (Maarten); M.L.C. van Veelen-Vincent (Marie-Lise); I.M.J. Mathijssen (Irene)

    2012-01-01

    textabstractPurpose: Brain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have

  5. Globus Pallidus Interna Deep Brain Stimulation in a Patient with Medically Intractable Meige Syndrome

    Directory of Open Access Journals (Sweden)

    Dae-Woong Bae

    2014-10-01

    Full Text Available Medical therapies in patients with Meige syndrome, including botulinum toxin injection, have been limited because of incomplete response or adverse side effects. We evaluated a patient with Meige syndrome who was successfully treated with deep brain stimulation (DBS in the globus pallidus interna (GPi. This case report and other previous reports suggest that bilateral GPi DBS may be an effective treatment for medically refractory Meige syndrome, without significant adverse effects.

  6. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  7. Brain hemorrhages in Jacobsen syndrome: A retrospective review of six cases and clinical recommendations.

    Science.gov (United States)

    Grossfeld, Paul

    2017-03-01

    Jacobsen syndrome is a rare chromosomal disorder caused by distal deletions in the long arm of chromosome 11. All patients with Jacobsen syndrome have Paris-Trousseau syndrome, a bleeding disorder that causes neonatal thrombocytopenia, and persistent platelet dysfunction. Despite that, to date there are no reported cases of hemorrhagic strokes occurring in patients with Jacobsen syndrome. In the last 6 years at least six cases of brain hemorrhages in patients with Jacobsen syndrome have occurred. In this report, we perform a retrospective review of these six cases. The analysis indicates that the etiology of brain hemorrhages in Jacobsen syndrome is likely multifactorial. A likely cause (or causes) was identified in three of the cases, and additional potential risk factors were identified. Based on these findings, clinical recommendations are provided that should aid in the identification of those individuals with Jacobsen syndrome that are at increased risk for brain hemorrhages, and will hopefully decrease the occurrence of this devastating complication in people with Jacobsen syndrome.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Terson syndrome in subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury.

    Science.gov (United States)

    Czorlich, Patrick; Skevas, Christos; Knospe, Volker; Vettorazzi, Eik; Richard, Gisbert; Wagenfeld, Lars; Westphal, Manfred; Regelsberger, Jan

    2015-01-01

    This prospective trial was designed to evaluate the incidence of Terson syndrome in patients suffering from subarachnoid hemorrhage, intracerebral hemorrhage, or traumatic brain injury and whether consequences necessarily derive from the intraocular hemorrhage itself. Two ophthalmologic examinations were performed to identify patients with Terson syndrome. Data on initial Glasgow Coma Scale, Hunt and Hess and Fisher grades, aneurysm site and diameter, and volume of hemorrhage in intracerebral hemorrhage patients were correlated to the location and course of Terson syndrome. Follow-up was performed after 3 months, including clinical and ophthalmologic investigations. The data showed that 16 of 83 subarachnoid hemorrhage patients (19.3%), 2 of 22 intracerebral hemorrhage patients (9.1%), and 1 of 32 traumatic brain injury patients (3.1%) suffered from Terson syndrome. Low Glasgow Coma Scale (p = 0.002), high Hunt and Hess grade (p Terson syndrome. The neurological outcome in subarachnoid hemorrhage patients suffering from Terson syndrome was worse compared with that of subarachnoid hemorrhage patients without Terson syndrome (p = 0.005), and vitrectomy was performed in seven eyes of six patients due to poor visual acuity. Terson syndrome is underestimated in patients with subarachnoid hemorrhage and a rare pathology in intracerebral hemorrhage as well as in traumatic brain injury patients. Spontaneous regression of the intraocular hemorrhage may be seen, but in half of the patients, vitrectomy is necessary to prevent permanent visual deterioration.

  9. Epitaxial overgrowth of II-VI compounds on patterned substrates

    Energy Technology Data Exchange (ETDEWEB)

    Schikora, D. (Inst. fuer Halbleiterphysik und Optik, Technische Univ. Braunschweig, Braunschweig (Germany)); Hausleitner, H. (Forschungsinst. fuer Optoelektronik, Univ. Linz (Austria)); Einfeldt, S. (and others)

    1994-04-14

    The selected area epitaxial overgrowth of narrow gap HgTe as well as wide gap CdTe and ZnTe on CdTe/GaAs substrates, which had been structured by dry etching techniques, has been investigated. A plasma etching process using a barrel reactor with CH[sub 4]-H[sub 2] gases has been employed to prepare stripes with a width of about 1 [mu]m with anisotropic as well as isotropic etching profiles. It has been found, that the selected area HgTe overgrowth takes place with a high local selectivity to the low index planes of the patterned surface. In contrast, the selected area overgrowth of the wide gap CdTe and ZnTe is controlled by anisotropic growth kinetics provided that the substrate temperature is not lower than 220[sup o]C and the starting surface consists of well developed low index crystallographic planes

  10. Axonal dystrophy in the brain of mice with Sanfilippo syndrome.

    Science.gov (United States)

    Beard, Helen; Hassiotis, Sofia; Gai, Wei-Ping; Parkinson-Lawrence, Emma; Hopwood, John J; Hemsley, Kim M

    2017-09-01

    Axonal dystrophy has been described as an early pathological feature of neurodegenerative disorders including Alzheimer's disease and amyotrophic lateral sclerosis. Axonal inclusions have also been reported to occur in several neurodegenerative lysosomal storage disorders including Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome). This disorder results from a mutation in the gene encoding the lysosomal sulphatase sulphamidase, and as a consequence heparan sulphate accumulates, accompanied by secondarily-stored gangliosides. The precise basis of symptom generation in MPS IIIA has not been elucidated, however axonal dystrophy may conceivably lead to impaired vesicular trafficking, neuronal dysfunction and/or death. We have utilised a faithful murine model of MPS IIIA to determine the spatio-temporal profile of neuronal inclusion formation and determine the effect of restoring normal lysosomal function. Dopaminergic (tyrosine hydroxylase-positive), cholinergic (choline acetyltransferase-positive) and GABAergic (glutamic acid decarboxylase65/67-positive) neurons were found to exhibit axonal dystrophy in MPS IIIA mouse brain. Axonal lesions present by ~seven weeks of age were Rab5-positive but lysosomal integral membrane protein-2 negative, suggesting early endosomal involvement. By 9-12-weeks of age, immunoreactivity for the autophagosome-related proteins LC3 and p62 and the proteasomal subunit 19S was noted in the spheroidal structures, together with wildtype α-synuclein, phosphorylated Thr-181 Tau and amyloid precursor protein, indicative of impaired axonal trafficking. Sulphamidase replacement reduced but did not abrogate the axonal lesions. Therefore, if axonal dystrophy impairs neuronal activity and ultimately, neuronal function, its incomplete resolution warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Proteus syndrome review: molecular, clinical, and pathologic features.

    Science.gov (United States)

    Cohen, M Michael

    2014-02-01

    Proteus syndrome is caused by an activating AKT1 mutation (c.49G>A, p.Glu17Lys). Many variable features are possible in this mosaic disorder, including: (i) disproportionate, asymmetric, and distorting overgrowth; (ii) bone abnormalities different from those observed in other disorders; (iii) a characteristic cerebriform connective tissue nevus made up of highly collagenized connective tissue; (iv) epidermal nevi in early life, consisting of acanthosis and hyperkeratosis; (v) vascular malformations of the capillary, venous, or lymphatic types; (vi) dysregulated adipose tissue including lipomas, lipohypoplasia, fatty overgrowth, and localized fat deposits; (vii) other unusual features, including bullous lung alterations; specific neoplasms; a facial phenotype associated with intellectual disability and/or seizures, and/or brain malformations; and (viii) deep vein thrombosis, resulting in premature death. Concluding remarks address diagnostic criteria, natural history, management, psychosocial issues, and differential diagnosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Prenatal pharmacotherapy rescues brain development in a Down's syndrome mouse model.

    Science.gov (United States)

    Guidi, Sandra; Stagni, Fiorenza; Bianchi, Patrizia; Ciani, Elisabetta; Giacomini, Andrea; De Franceschi, Marianna; Moldrich, Randal; Kurniawan, Nyoman; Mardon, Karine; Giuliani, Alessandro; Calzà, Laura; Bartesaghi, Renata

    2014-02-01

    Intellectual impairment is a strongly disabling feature of Down's syndrome, a genetic disorder of high prevalence (1 in 700-1000 live births) caused by trisomy of chromosome 21. Accumulating evidence shows that widespread neurogenesis impairment is a major determinant of abnormal brain development and, hence, of intellectual disability in Down's syndrome. This defect is worsened by dendritic hypotrophy and connectivity alterations. Most of the pharmacotherapies designed to improve cognitive performance in Down's syndrome have been attempted in Down's syndrome mouse models during adult life stages. Yet, as neurogenesis is mainly a prenatal event, treatments aimed at correcting neurogenesis failure in Down's syndrome should be administered during pregnancy. Correction of neurogenesis during the very first stages of brain formation may, in turn, rescue improper brain wiring. The aim of our study was to establish whether it is possible to rescue the neurodevelopmental alterations that characterize the trisomic brain with a prenatal pharmacotherapy with fluoxetine, a drug that is able to restore post-natal hippocampal neurogenesis in the Ts65Dn mouse model of Down's syndrome. Pregnant Ts65Dn females were treated with fluoxetine from embryonic Day 10 until delivery. On post-natal Day 2 the pups received an injection of 5-bromo-2-deoxyuridine and were sacrificed after either 2 h or after 43 days (at the age of 45 days). Untreated 2-day-old Ts65Dn mice exhibited a severe neurogenesis reduction and hypocellularity throughout the forebrain (subventricular zone, subgranular zone, neocortex, striatum, thalamus and hypothalamus), midbrain (mesencephalon) and hindbrain (cerebellum and pons). In embryonically treated 2-day-old Ts65Dn mice, precursor proliferation and cellularity were fully restored throughout all brain regions. The recovery of proliferation potency and cellularity was still present in treated Ts65Dn 45-day-old mice. Moreover, embryonic treatment restored

  13. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain.

    Science.gov (United States)

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María; García-Vallejo, Felipe

    2014-01-01

    The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.

  14. Unilateral vestibular schwannoma and meningiomas in a patient with PIK3CA-related segmental overgrowth: Co-occurrence of mosaicism for 2 rare disorders.

    Science.gov (United States)

    Mills, J R; Moyer, A M; Kipp, B R; Poplawski, A B; Messiaen, L M; Babovic-Vuksanovic, D

    2018-01-01

    A 28-year-old female with PIK3CA-related segmental overgrowth presented with headaches. She also had a unilateral vestibular schwannoma (VS), as well as 3 small (A (p.Gly914Arg) mutation, confirming the diagnosis of PIK3CA-related overgrowth, but no mutations in NF2 were detected. Although VS has not previously been reported in PIK3CA-related segmental overgrowth, meningiomas have, raising the question of whether this patient's VS and meningiomas represent coincidental NF2 or phenotypic extension of her overgrowth syndrome. Genetic analysis of the VS revealed a heterozygous NF2 mutation c.784C>T (p.Arg262Ter) and loss of a portion of 22q, including NF2, SMARCB1, and LZTR1 genes. These results suggest that the patient has 2 different mosaic disorders, NF2 and PIK3CA-related overgrowth. The PIK3CA mutation was also present in the VS. Confirmation of the clinical diagnosis of mosaic NF2 in this patient has implications for monitoring and highlights the possibility of co-occurrence of mosaicism for multiple rare disorders in a single patient. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

    Science.gov (United States)

    Martinez-Ramirez, Daniel; Jimenez-Shahed, Joohi; Leckman, James Frederick; Porta, Mauro; Servello, Domenico; Meng, Fan-Gang; Kuhn, Jens; Huys, Daniel; Baldermann, Juan Carlos; Foltynie, Thomas; Hariz, Marwan I; Joyce, Eileen M; Zrinzo, Ludvic; Kefalopoulou, Zinovia; Silburn, Peter; Coyne, Terry; Mogilner, Alon Y; Pourfar, Michael H; Khandhar, Suketu M; Auyeung, Man; Ostrem, Jill Louise; Visser-Vandewalle, Veerle; Welter, Marie-Laure; Mallet, Luc; Karachi, Carine; Houeto, Jean Luc; Klassen, Bryan Timothy; Ackermans, Linda; Kaido, Takanobu; Temel, Yasin; Gross, Robert E; Walker, Harrison C; Lozano, Andres M; Walter, Benjamin L; Mari, Zoltan; Anderson, William S; Changizi, Barbara Kelly; Moro, Elena; Zauber, Sarah Elizabeth; Schrock, Lauren E; Zhang, Jian-Guo; Hu, Wei; Rizer, Kyle; Monari, Erin H; Foote, Kelly D; Malaty, Irene A; Deeb, Wissam; Gunduz, Aysegul; Okun, Michael S

    2018-01-16

    Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Scores on the Yale Global Tic Severity Scale and adverse events. The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

  16. Specific and evolving resting-state network alterations in post-concussion syndrome following mild traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Arnaud Messé

    Full Text Available Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1-3 weeks and late (6 months phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients.

  17. Upregulation of lysyl oxidase expression in cyclosporin A-induced gingival overgrowth

    Directory of Open Access Journals (Sweden)

    Chung-Hung Tsai

    2009-03-01

    Conclusion: LOX expression was significantly upregulated in CsA-induced gingival overgrowth specimens. In addition, the expression of LOX increased with the grade of inflammation in CsA-induced gingival overgrowth.

  18. Size and shape control in the overgrowth of gold nanorods

    Science.gov (United States)

    Ratto, Fulvio; Matteini, Paolo; Rossi, Francesca; Pini, Roberto

    2010-08-01

    We report on a new sustainable approach to manipulate the optical behaviour and geometrical properties of gold nanorods in aqueous solutions by fine control of their overgrowth. In our approach, the overgrowth is realized by modulation of the reduction of the gold ions which are left as Au1+ after the primary step of the synthesis (typically as much as 80% of the gold ions available in the growth solution). The progress of the reduction requires the gradual addition of ascorbic acid, which transforms the Au1+ into Au0 and may be performed in the original growth solution with no need for any further manipulation. By control of the total amount and rate of administration of the ascorbic acid, we prove the possibility to realize a systematic modulation of the average lengths, diameters, shapes (rod or dog-bone like), and light extinction of the nanoparticles. A slow overgrowth leads to a gradual enlargement of the lengths and diameters at almost constant shape. In contrast, a faster overgrowth results into a more complex modification of the overall shape of the gold nanorods.

  19. Multispectral Brain Morphometry in Tourette Syndrome Persisting into Adulthood

    Science.gov (United States)

    Draganski, Bogdan; Martino, Davide; Cavanna, Andrea E.; Hutton, Chloe; Orth, Michael; Robertson, Mary M.; Critchley, Hugo D.; Frackowiak, Richard S.

    2010-01-01

    Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into…

  20. Genetics Home Reference: Gorlin syndrome

    Science.gov (United States)

    ... delayed development, intellectual disability, overgrowth of the body (macrosomia), and other physical abnormalities. Researchers believe that these ... Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay. Am J Med Genet A. ...

  1. Acute brain ischemia as a complication of the Ehlers-Danlos syndrome, the case series.

    Science.gov (United States)

    Pajak, Michal; Majos, Marcin A; Szubert, Wojciech; Stefanczyk, Ludomir; Majos, Agata

    2014-10-01

    Vascular type of Ehlers-Danlos syndrome involves many severe complications leading not only to organ-specific symptoms but often ends in a sudden death. The aim of this paper was to present a diagnostic possibilities and its efficiency rate in patients with vascular complications of Ehlers-Danlos syndrome who suffered from artery dissection resulting in acute brain or limb ischemia. We analysed three patients with diagnosed Ehlers-Danlos syndrome who were referred to radiology department for diagnostic imaging of affected vascular beds, each experienced brain ischemia. The paper also aims at offering some general recommendations for patients suffering from possible complications of type IV Ehlers-Danlos syndrome basing on our own experience and available literature data. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. SHOCK SYNDROME IN A PATIENT WITH HYPOPITUITARISM DUE TO BRAIN TUMOR

    Directory of Open Access Journals (Sweden)

    Andreja Sinkovič

    2004-04-01

    Full Text Available Background. Shock syndrome is an acute tissue hypoperfusion. Early diagnosis and adequate symptomatic and causal treatment are mandatory. In spite of different etiologies (dehidration, bleeding, heart failure, sepsis, clinical signs and symptomes are similar (hypotension, tachicardia, tachipnoe, pallor, cold and wet skin, oliguria and metabolic acidosis. Rarely, the shock syndrome is the consequence of the adrenal insufficiency due to hypopituitarism caused by brain tumor where early treatment with hydrocortisone is urgent.Methods. This article presents a patient with a shock syndrome and multiorgan failure. Endocrinological testing and brain CT demonstrated an endocrinologically inactive tumor of hypophysis. The tumor was growing into adjacent hypophyseal tissue and causing hypopituitarism with secondary hypothyroidism and adrenal insufficiency and deficit of both gonadotropins and growth hormone.Conclusions. Primary or secondary adrenal insufficiency are among rare causes of shock syndrome. Whenever it is suspected, estimation of serum levels of cortisol and ACTH is necessary and immediate treatment with hydrocortisone should be instituted.

  3. Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.

    Science.gov (United States)

    Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Macià, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

    2015-03-01

    Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Small intestinal bacterial overgrowth in patients with rheumatoid arthritis.

    Science.gov (United States)

    Henriksson, A E; Blomquist, L; Nord, C E; Midtvedt, T; Uribe, A

    1993-01-01

    OBJECTIVES--To examine the microflora of the upper small intestine in patients with seropositive rheumatoid arthritis (RA) using a combination of microbial cultivation and tests for microbial metabolic activity. METHODS--Twenty five patients with seropositive RA, 12 achlorhydric control subjects, and 11 control subjects with normal gastric acid secretion were investigated. Disease activity was evaluated in the patients with RA by three different indices. Eight (32%) of the patients with RA had hypochlorhydria or achlorhydria. The acid secretory capacity was determined with pentagastrin stimulation. A modified Crosby capsule was used to obtain biopsy specimens and samples of intestinal fluid from the proximal jejunum; aerobic and anaerobic microbial cultivation of mucosal specimens/intestinal fluid was carried out, and gas production and microflora associated characteristics in jejunal fluid were determined. Additionally, a bile acid deconjugation breath test was performed. RESULTS--Subjects with at least one of the following findings were considered to have bacterial overgrowth: positive bile acid deconjugation test; growth of Enterobacteriaceae; positive gas production; or low tryptic activity. By these criteria half of the patients with RA with hypochlorhydria or achlorhydria and half of the achlorhydric controls had bacterial overgrowth. Thirty five per cent of the patients with RA with normal gastric acid secretion had bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in patients with RA with bacterial overgrowth than in those without. CONCLUSIONS--A high frequency of small intestinal bacterial overgrowth was found in patients with RA; it was associated with a high disease activity and observed in patients with hypochlorhydria or achlorhydria and in those with normal acid secretion. PMID:8346978

  5. Nerve growth factor metabolic dysfunction in Down’s syndrome brains

    Science.gov (United States)

    Iulita, M. Florencia; Do Carmo, Sonia; Ower, Alison K.; Fortress, Ashley M.; Aguilar, Lisi Flores; Hanna, Michael; Wisniewski, Thomas; Granholm, Ann-Charlotte; Buhusi, Mona; Busciglio, Jorge

    2014-01-01

    Basal forebrain cholinergic neurons play a key role in cognition. This neuronal system is highly dependent on NGF for its synaptic integrity and the phenotypic maintenance of its cell bodies. Basal forebrain cholinergic neurons progressively degenerate in Alzheimer’s disease and Down’s syndrome, and their atrophy contributes to the manifestation of dementia. Paradoxically, in Alzheimer’s disease brains, the synthesis of NGF is not affected and there is abundance of the NGF precursor, proNGF. We have shown that this phenomenon is the result of a deficit in NGF’s extracellular metabolism that compromises proNGF maturation and exacerbates its subsequent degradation. We hypothesized that a similar imbalance should be present in Down’s syndrome. Using a combination of quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting and zymography, we investigated signs of NGF metabolic dysfunction in post-mortem brains from the temporal (n = 14), frontal (n = 34) and parietal (n = 20) cortex obtained from subjects with Down’s syndrome and age-matched controls (age range 31–68 years). We further examined primary cultures of human foetal Down’s syndrome cortex (17–21 gestational age weeks) and brains from Ts65Dn mice (12–22 months), a widely used animal model of Down’s syndrome. We report a significant increase in proNGF levels in human and mouse Down’s syndrome brains, with a concomitant reduction in the levels of plasminogen and tissue plasminogen activator messenger RNA as well as an increment in neuroserpin expression; enzymes that partake in proNGF maturation. Human Down’s syndrome brains also exhibited elevated zymogenic activity of MMP9, the major NGF-degrading protease. Our results indicate a failure in NGF precursor maturation in Down’s syndrome brains and a likely enhanced proteolytic degradation of NGF, changes which can compromise the trophic support of basal forebrain cholinergic

  6. The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study

    Directory of Open Access Journals (Sweden)

    Iris Zavoreo

    2017-01-01

    Full Text Available Objective: Burning mouth syndrome (BMS is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. The results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. Methods: By use of transcranial sonography of the brain parenchyma, substantia nigra, midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years and 20 controls with chronic pain in the lumbosacral region (61.5±15. Statistical analysis was performed by use of Student t test with significance set at p<0.05. Results: The results of this study have shown hypoechogenicity of the substantia nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS patients (p<0,05 as compared to controls. Conclusions: Altered transcranial sonography findings of the brain parenchyma, midbrain raphe and brain nucleus in patients with burning mouth syndrome might reflect central disturbances within this syndrome.

  7. Sotos syndrome

    OpenAIRE

    A Juneja; Sultan, A.

    2007-01-01

    Abstract Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications...

  8. Proteus syndrome

    Directory of Open Access Journals (Sweden)

    Debi Basanti

    2005-01-01

    Full Text Available Proteus syndrome is a variable and complex disorder characterized by multifocal overgrowths affecting any tissue or structure of the body. We present a girl aged 3 years and 8 months with an epidermal nevus, port-wine stain, macrodactyly with gigantism of the feet, lymphohemagiomas and multiple lipomas.

  9. Surgical treatment for ~brain compartment syndrome' in children ...

    African Journals Online (AJOL)

    Objectives. Traumatic brain injury accounts for a high percentage of deaths in children. Raised intracranial pressure (ICP) due to brain swelling within the closed compartment of the skull leads to death or severe neurological disability if not effectively treated. We report our experience with 12 children who presented with ...

  10. Epidermal Nevus Syndrome Associated with Brain Malformations and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-01-01

    Full Text Available Researchers at Juntendo University and Tokyo Women’s Medical University, Japan; and University of California, San Francisco, Ca, report a male infant with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

  11. [On the question of the organization of brain function: cortical associations, «disconnection» syndrome and higher brain functions].

    Science.gov (United States)

    Damulin, I V

    2015-01-01

    The review considers the structural/functional brain organization, the disturbance of which is accompanied by the development of cognitive and behavioral disorders. The significance of the disruption of parallel circuits connecting frontal lobes with subcortical structures (the basal ganglia, thalamus, cerebellum) is highlighted. This disruption is clinically described as "disconnection" syndrome. The associations between the basal ganglia and the cortex of the large cerebral hemispheres responsible for motor, cognitive and emotional/behavioral functions do not restricted to these spheres and is characteristic not only of frontal brain areas. There are circuits connecting other brain compartments and the basal ganglia that provide perception, and are involved in decision making on the basis of input information of different modalities.The improvement of understanding of the pathophysiology and neurochemistry of these structures opens new possibilities for selective action on some or other circuit to achieve the best therapeutic result.

  12. Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline.

    Science.gov (United States)

    Cole, James H; Annus, Tiina; Wilson, Liam R; Remtulla, Ridhaa; Hong, Young T; Fryer, Tim D; Acosta-Cabronero, Julio; Cardenas-Blanco, Arturo; Smith, Robert; Menon, David K; Zaman, Shahid H; Nestor, Peter J; Holland, Anthony J

    2017-08-01

    Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [ 11 C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Posterior reversible encephalopathy syndrome and stroke after intravenous immunoglobulin treatment in Miller-Fisher syndrome/Bickerstaff brain stem encephalitis overlap syndrome.

    Science.gov (United States)

    Stetefeld, Henning R; Lehmann, Helmar C; Fink, Gereon R; Burghaus, Lothar

    2014-10-01

    The association of a posterior reversible encephalopathy syndrome (PRES) without arterial hypertension with autoimmune-mediated inflammatory neuropathies such as Guillain-Barré syndrome (GBS) is a rare and poorly understood phenomenon. To date, PRES has been described as initial manifestation, coincidental finding, or adverse event subsequent to immunomodulatory treatment with intravenous immunoglobulin (IVIG) in cases of axonal and demyelinating GBS as well as in Miller-Fisher syndrome (MFS). We here report a case of MFS/Bickerstaff brain stem encephalitis (BBE)-overlap syndrome and nonhypertensive PRES that occurred in close temporal association with IVIG treatment and caused stroke. Immunoadsorption ameliorated the disease course. Our case supports the notion that in severe cases, immunoadsorption should be considered as first-line therapy instead of IVIG for rapid removal of IgG and thus to hasten recovery and improve functional outcome. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Twiddler's syndrome in a patient with a deep brain stimulation device for generalized dystonia.

    Science.gov (United States)

    Astradsson, Arnar; Schweder, Patrick M; Joint, Carole; Green, Alexander L; Aziz, Tipu Z

    2011-07-01

    Deep brain stimulation (DBS) is the technique of neurostimulation of deep brain structures for the treatment of conditions such as essential tremor, dystonia, Parkinson's disease and chronic pain syndromes. The procedure uses implanted deep brain stimulation electrodes connected to extension leads and an implantable pulse generator (IPG). Hardware failure related to the DBS procedure is not infrequent, and includes electrode migration and disconnection. We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed. Radiographs showed multiple twisting of the extension leads with disconnection from the brain electrodes and a diagnosis of Twiddler's syndrome was made. Twiddler's syndrome was first described in patients with cardiac pacemakers. Patients with mental disability, elderly and obese patients are at increased risk. Twiddler's syndrome should be suspected whenever there is a failure of the DBS device to relieve symptoms previously responsive to stimulation. Surgical correction is usually required. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Clinico-Pathological Correlations of the Frontal Lobe Syndrome : Results of a Large Brain Bank Study

    NARCIS (Netherlands)

    Krudop, Welmoed A; Bosman, Sjanne; Geurts, Jeroen J G; Sikkes, Sietske A M; Verwey, Nicolaas A; Stek, Max L; Scheltens, Philip; Rozemuller, Annemieke J M; Pijnenburg, Yolande A L

    2015-01-01

    AIMS: A clinical frontal lobe syndrome (FLS) is generally attributed to functional or structural disturbances within frontal-subcortical circuits. We studied the distribution of pathological brain changes in FLS. Additionally, the prevalence of FLS among various disorders was studied. METHODS: We

  16. Trajectories of Early Brain Volume Development in Fragile X Syndrome and Autism

    Science.gov (United States)

    Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

    2012-01-01

    Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism. Method: The study included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically…

  17. Brief Report: CANTAB Performance and Brain Structure in Pediatric Patients with Asperger Syndrome

    Science.gov (United States)

    Kaufmann, Liane; Zotter, Sibylle; Pixner, Silvia; Starke, Marc; Haberlandt, Edda; Steinmayr-Gensluckner, Maria; Egger, Karl; Schocke, Michael; Weiss, Elisabeth M.; Marksteiner, Josef

    2013-01-01

    By merging neuropsychological (CANTAB/Cambridge Neuropsychological Test Automated Battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group…

  18. Association of Symptoms Following Mild Traumatic Brain Injury With Posttraumatic Stress Disorder vs Postconcussion Syndrome

    DEFF Research Database (Denmark)

    Lagarde, E.; Salmi, L. R.; Holm, L. W.

    2014-01-01

    IMPORTANCE A proportion of patients experience long-lasting symptoms following mild traumatic brain injury (MTBI). The postconcussion syndrome (PCS), included in the DSM-IV, has been proposed to describe this condition. Because these symptoms are subjective and common to other conditions, there i...

  19. Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

    DEFF Research Database (Denmark)

    Larsen, K.B.; Laursen, H.; Graem, N.

    2008-01-01

    Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

  20. Achille Louis Foville's atlas of brain anatomy and the Defoville syndrome.

    Science.gov (United States)

    Brogna, Christian; Fiengo, Leslie; Türe, Uğur

    2012-05-01

    Achille Louis Foville's atlas of brain anatomy (1844) is one of the most artistic and detailed works on neuroanatomy in the medical literature. The outstanding drawings by the 2 artists, Emile Beau and Frédéric-Michel Bion, highlight all the philosophy, ability, and sensibility of A.L. Foville in carefully dissecting the superficial and deep structures of the brain and spinal cord. Several plates show true brain fiber dissections of high artistic and academic value. As a result of an early misrecognition in the medical literature, "inferior Foville syndrome" has been wrongly attributed to Achille Louis Foville rather than his son, Achille Louis François Foville (1832-1887), also called Defoville. Therefore, we suggest that Defoville, who actually described the pontine syndrome for the first time in the neurological literature, deserves to be credited for this syndrome and that the syndrome should be called the Defoville syndrome. Through analyzing the political and scientific events in France in the 19th century, we highlight the invaluable contributions of A.L. Foville and his son to the history of neuroanatomy and neurology.

  1. Poly-epiphyseal overgrowth: description of a previously unreported skeletal dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Pazzaglia, Ugo E.; Bonaspetti, Giovanni [University of Brescia, Orthopaedic Clinic, Brescia (Italy); Beluffi, Giampiero [Fondazione IRCCS Policlinico San Matteo, Department of Paediatric Radiology, Pavia (Italy); Marchi, Antonietta; Bozzola, Mauro; Savasta, Salvatore [Fondazione IRCCS Policlinico San Matteo, Paediatric Clinic, University of Pavia, Pavia (Italy)

    2007-10-15

    A skeletal dysplasia with previously unreported features is presented. Its evolution was characterized by growth abnormalities of bones without involvement of other organs. Advanced bone age, increased stature and irregular epiphyseal ossification with stippling of the main long bones were documented. Physeal overgrowth was massive in the left proximal humerus and femur. Furthermore, the hip joint appeared fused with an abundant mass of pathological calcific tissue extending from the femur to the ilium. Pathological epiphyses were characterized by anarchic cartilaginous proliferation with multiple ossification centres, while lamellar bone apposition and remodelling were normal. The observed bone changes were different from those in any previously reported syndrome, metabolic defect or bone dysplasia. However, they clearly indicated a defect of endochondral ossification with some resemblance to phenotypes observed in dysplasia epiphysealis hemimelica. (orig.)

  2. Drug-induced gingival overgrowth: The nemesis of gingiva unravelled

    Directory of Open Access Journals (Sweden)

    Vipin Bharti

    2013-01-01

    Full Text Available Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of the gingiva due to an adverse drug reaction (ADR in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival enlargement develops, it affects the normal oral hygiene practice and may interfere with masticatory functions. It gradually becomes a source of pain and the condition often leads to disfiguration. Within the group of patients that develop this unwanted effect, there appears to be variability in the extent and severity of the gingival changes. It would seem pertinent to identify and explore possible risk factors and relating them with the treatment plan. This article throws light on respective drugs and their association with gingival overgrowth and approaches to treatment based on current knowledge and investigative observations.

  3. Drug-induced gingival overgrowth: The nemesis of gingiva unravelled.

    Science.gov (United States)

    Bharti, Vipin; Bansal, Chhaya

    2013-03-01

    Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of the gingiva due to an adverse drug reaction (ADR) in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival enlargement develops, it affects the normal oral hygiene practice and may interfere with masticatory functions. It gradually becomes a source of pain and the condition often leads to disfiguration. Within the group of patients that develop this unwanted effect, there appears to be variability in the extent and severity of the gingival changes. It would seem pertinent to identify and explore possible risk factors and relating them with the treatment plan. This article throws light on respective drugs and their association with gingival overgrowth and approaches to treatment based on current knowledge and investigative observations.

  4. Small Intestinal Bacterial Overgrowth: A Case-Based Review

    OpenAIRE

    Kristen H. Reynolds

    2015-01-01

    Small intestinal bacterial overgrowth (SIBO) is a condition of increased microbial load in the small intestine. The microbes feed on dietary carbohydrates and starches via fermentation, leading to gas production, inflammation and damage to the lining of the small intestine. Clinical presentation is varied, including abdominal pain, bloating, malabsorption and systemic symptoms. SIBO is associated with many challenging and chronic conditions such as fibromyalgia, chronic fatigue and chronic pa...

  5. Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development.

    Science.gov (United States)

    Koran, Mary Ellen I; Hohman, Timothy J; Edwards, Courtney M; Vega, Jennifer N; Pryweller, Jennifer R; Slosky, Laura E; Crockett, Genea; Villa de Rey, Lynette; Meda, Shashwath A; Dankner, Nathan; Avery, Suzanne N; Blackford, Jennifer U; Dykens, Elisabeth M; Thornton-Wells, Tricia A

    2014-01-01

    Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS. High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE. Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE ϵ4 carrier status were associated with LILV and RILV volume. Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS-specific neurodegenerative processes, as opposed to general

  6. Tc-99m HMPAO brain SPECT scanning in Munchausen syndrome.

    Science.gov (United States)

    Mountz, J M; Parker, P E; Liu, H G; Bentley, T W; Lill, D W; Deutsch, G

    1996-01-01

    Regional cerebral blood flow was studied in a patient with Munchausen syndrome using high resolution Tc-99m HMPAO SPECT. The scan demonstrated marked hyperperfusion of the right hemithalamus. The cranial CT scan was normal. The abnormal right hemithalamic blood flow is discussed in relation to the hypothesized neuropathy of this disorder. Images Figure 1 Figure 2 Figure 3 PMID:8580117

  7. Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders.

    Science.gov (United States)

    Theoharides, Theoharis C; Athanassiou, Marianna; Panagiotidou, Smaro; Doyle, Robert

    2015-02-15

    Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, seizures, stress, and treatment. There are a number of intriguing differences and similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear to distinguish Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective BDNF signaling. Moreover, brain mast cell (MC) activation and focal inflammation may be more prominent in ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of luteolin or other natural molecules may be useful in the treatment of Rett syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Marble brain syndrome: osteopetrosis, renal acidosis and calcification of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Jacquemin, C.; Mullaney, P.; Svedberg, E. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    1998-10-01

    Cerebral calcification in children is frequently associated with systemic metabolic disease. We present a case of ``marble brain syntrome``, which showed this abnormality. (orig.) (orig.) With 2 figs.

  9. Differential Diagnosis Tool for Parkinsonian Syndrome Using Multiple Structural Brain Measures

    Directory of Open Access Journals (Sweden)

    Miho Ota

    2013-01-01

    Full Text Available Clinical differentiation of parkinsonian syndromes such as the Parkinson variant of multiple system atrophy (MSA-P and cerebellar subtype (MSA-C from Parkinson's disease is difficult in the early stage of the disease. To identify the correlative pattern of brain changes for differentiating parkinsonian syndromes, we applied discriminant analysis techniques by magnetic resonance imaging (MRI. T1-weighted volume data and diffusion tensor images were obtained by MRI in eighteen patients with MSA-C, 12 patients with MSA-P, 21 patients with Parkinson’s disease, and 21 healthy controls. They were evaluated using voxel-based morphometry and tract-based spatial statistics, respectively. Discriminant functions derived by step wise methods resulted in correct classification rates of 0.89. When differentiating these diseases with the use of three independent variables together, the correct classification rate was the same as that obtained with step wise methods. These findings support the view that each parkinsonian syndrome has structural deviations in multiple brain areas and that a combination of structural brain measures can help to distinguish parkinsonian syndromes.

  10. Proteus syndrome in adulthood

    NARCIS (Netherlands)

    Muller, E; Lichtendahl, DHE; Hofer, SOP

    Proteus syndrome is a very rare congenital condition comprising malformations and overgrowth of multiple sorts of tissue. It was described for the first time in 1979 and was termed Proteus syndrome in 1983. The authors describe a 37-year-old patient who was diagnosed initially as having

  11. Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration.

    Science.gov (United States)

    Morley, Wendy A; Seneff, Stephanie

    2014-01-01

    The number of sports-related concussions has been steadily rising in recent years. Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading to increased susceptibility to previously considered innocuous concussion. We discuss how modern day environmental toxicant exposure, along with major changes in our food supply and lifestyle practices, profoundly reduce the bioavailability of neuro-critical nutrients such that the normal processes of homeostatic balance and resilience are no longer functional. Their diminished capacity triggers physiological and biochemical 'work around' processes that result in undesirable downstream consequences. Exposure to certain environmental chemicals, particularly glyphosate, the active ingredient in the herbicide, Roundup(®), may disrupt the body's innate switching mechanism, which normally turns off the immune response to brain injury once danger has been removed. Deficiencies in serotonin, due to disruption of the shikimate pathway, may lead to impaired melatonin supply, which reduces the resiliency of the brain through reduced antioxidant capacity and alterations in the cerebrospinal fluid, reducing critical protective buffering mechanisms in impact trauma. Depletion of certain rare minerals, overuse of sunscreen and/or overprotection from sun exposure, as well as overindulgence in heavily processed, nutrient deficient foods, further compromise the brain's resilience. Modifications to lifestyle practices, if widely implemented, could significantly reduce this trend of neurological damage.

  12. Posttraumatic refractory intracranial hypertension and brain herniation syndrome: cerebral hemodynamic assessment before decompressive craniectomy.

    Science.gov (United States)

    Bor-Seng-Shu, Edson; Paiva, Wellingson Silva; Figueiredo, Eberval G; Fujimoto, Yasunori; de Andrade, Almir Ferreira; Fonoff, Erich Talamoni; Teixeira, Manoel Jacobsen

    2013-01-01

    The pathophysiology of traumatic brain swelling remains little understood. An improved understanding of intracranial circulatory process related to brain herniation may have treatment implications. To investigate the cerebral hemodynamic changes associated with brain herniation syndrome due to traumatic brain swelling. Nineteen head-injured patients with evidence of refractory intracranial hypertension and transtentorial herniation were prospectively studied. Cerebral hemodynamic assessment by transcranial Doppler (TCD) ultrasonography was performed prior to decompressive craniectomy. Patients and their cerebral hemispheres were classified according to TCD-hemodynamic patterns, and the data correlated with neurological status, midline shift on CT scan, and Glasgow outcome scale scores at 6 months after injury. A wide variety of cerebral hemodynamic findings were observed. Ten patients (52.7%) presented with cerebral oligoemia, 3 patients (15.8%) with cerebral hyperemia, and 6 patients with nonspecific circulatory pattern. Circulatory disturbances were more frequently found in the side of maximal cerebral swelling than in the opposite side. Pulsatility index (PI) values suggested that ICP varied from acceptable to considerably high; patients with increased PI, indicating higher microvascular resistance. No correlation was found between cerebral hemodynamic findings and outcome. There is a marked heterogeneity of cerebral hemodynamic disturbances among patients with brain herniation syndrome.

  13. Deep Brain Stimulation for the Treatment of Dejerine-Roussy Syndrome.

    Science.gov (United States)

    Ward, Max; Mammis, Antonios

    2017-01-01

    Patients who suffer from Dejerine-Roussy syndrome commonly experience severe poststroke hemibody pain which has historically been attributed to thalamic lesions. Despite pharmacological treatment, a significant proportion of the population is resistant to traditional therapy. Deep brain stimulation is often appropriate for the treatment of resistant populations. In this review we aim to summarize the targets that are used to treat Dejerine-Roussy syndrome and provide insight into their clinical efficacy. In reviewing the literature, we defined stimulation success as achievement of a minimum of 50% pain relief. Contemporary targets for deep brain stimulation are the ventral posterior medial/ventral posterior lateral thalamic nuclei, periaqueductal/periventricular gray matter, the ventral striatum/anterior limb of the internal capsule, left centromedian thalamic nuclei, the nucleus ventrocaudalis parvocellularis internis, and the posterior limb of the internal capsule. Due to technological advancements in deep brain stimulation, its therapeutic effects must be reevaluated. Despite a lack of controlled evidence, deep brain stimulation has been effectively used as a therapeutic in clinical pain management. Further clinical investigation is needed to definitively evaluate the therapeutic efficacy of deep brain stimulation in treating the drug-resistant patient population. © 2017 S. Karger AG, Basel.

  14. Posttraumatic Refractory Intracranial Hypertension and Brain Herniation Syndrome: Cerebral Hemodynamic Assessment before Decompressive Craniectomy

    Directory of Open Access Journals (Sweden)

    Edson Bor-Seng-Shu

    2013-01-01

    Full Text Available Background. The pathophysiology of traumatic brain swelling remains little understood. An improved understanding of intracranial circulatory process related to brain herniation may have treatment implications. Objective. To investigate the cerebral hemodynamic changes associated with brain herniation syndrome due to traumatic brain swelling. Methods. Nineteen head-injured patients with evidence of refractory intracranial hypertension and transtentorial herniation were prospectively studied. Cerebral hemodynamic assessment by transcranial Doppler (TCD ultrasonography was performed prior to decompressive craniectomy. Patients and their cerebral hemispheres were classified according to TCD-hemodynamic patterns, and the data correlated with neurological status, midline shift on CT scan, and Glasgow outcome scale scores at 6 months after injury. Results. A wide variety of cerebral hemodynamic findings were observed. Ten patients (52.7% presented with cerebral oligoemia, 3 patients (15.8% with cerebral hyperemia, and 6 patients with nonspecific circulatory pattern. Circulatory disturbances were more frequently found in the side of maximal cerebral swelling than in the opposite side. Pulsatility index (PI values suggested that ICP varied from acceptable to considerably high; patients with increased PI, indicating higher microvascular resistance. No correlation was found between cerebral hemodynamic findings and outcome. Conclusions. There is a marked heterogeneity of cerebral hemodynamic disturbances among patients with brain herniation syndrome.

  15. Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome.

    Science.gov (United States)

    de Clercq, Nicolien C; Frissen, Myrthe N; Groen, Albert K; Nieuwdorp, Max

    2017-10-01

    Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome. A selective literature review was conducted to evaluate GI and brain interactions. Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear. One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.

  16. Diurnal variation in Cotard's syndrome (copresent with Capgras delusion) following traumatic brain injury.

    Science.gov (United States)

    Butler, P V

    2000-08-01

    The aim of this paper is to document regular nocturnal intensification of delusional nihilistic and persecutory ideas (Cotard delusion) linked with extreme depersonalisation and hypervivid dreaming. A 17-year-old man presented with Cotard and Capgras delusions after sustaining multiple cognitive impairments secondary to traumatic brain injury. Delusional ideation fully resolved within 14 days of commencement of olanzapine 5 mg daily. This patient's experience of perceptual abnormalities and impairments in meta-abilities related to self-monitoring and critical inferencing lends support to multicomponent sensory processing accounts of brain injury related, content-specific delusional syndromes.

  17. [Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

    Science.gov (United States)

    Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

    2018-01-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and chronic widespread pain. By using positron emission tomography, our study demonstrated neuroinflammation in the brain of patients with ME/CFS. Neuroinflammation was found to be widespread in the brain areas of the patients with ME/CFS and was associated with the severity of their neuropsychological symptoms. The ongoing research would lead to the establishment of objective diagnostic criteria and development of an appropriate therapy.

  18. Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.

    Science.gov (United States)

    Lin, Peijie; Nicholls, Laura; Assareh, Hassan; Fang, Zhiming; Amos, Timothy G; Edwards, Richard J; Assareh, Amelia A; Voineagu, Irina

    2016-06-06

    MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

  19. Growth of Gallium Nitride Nanorods and Their Coalescence Overgrowth

    Science.gov (United States)

    2012-09-07

    radiation angle dependence [13]. Sixth, GaN NR growth and coalescence overgrowth can result in a GaN thin film of significantly improved crystal quality...their work, by depositing the quantum structures on the GaN NRs of truncated pyramidal tops, InGaN layers of unclear quantum structures and crystal ...W. M. Chang, C. H. Liao, C. H. Lin, K. C. Shen, C. C. Yang, M. C. Hsu, J. H. Yeh, and T. C. Hsu, “Threading dislocation evolution in patterned GaN

  20. Hind brain agenesis a rare imaging findings in cerebro cerebellar lissencephalic syndrome.

    Science.gov (United States)

    Mundaganur, Praveen M; Solwalkar, Pradeep; Nimbal, Vishal

    2014-01-01

    A case report of cerebro cerebellar lissencephaly shows complete agenesis of cerebellum and brainstem which is rare imaging finding of group lissencephaly (type I lissencephaly). Though agenesis of cerebellum and brainstem were included in literature, in most of the cases we saw a hypoplasia or atrophy of cerebellum in lissencephaly syndrome. The CT scan findings of this patient shows features of lissencephaly with complete agenesis of brain stem and cerebellum associated with multiple congenital abnormalities.

  1. Cardiotocographic and Doppler Ultrasonographic Findings in a Fetus with Brain Death Syndrome

    OpenAIRE

    Chen, Yi-Ting; Hsu, Shih-Tien; Tseng, Jenn-Jhy; Chen, Wei-Chih; Ho, Esther Shih-Chu; Chou, Min-Min

    2006-01-01

    Objective: The diagnosis of brain death syndrome by cardiotocography (CTG) and Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation. Case Report: A 23-year-old, gravida 2, para 0, woman was referred to our hospital because of the absence of fetal movements. CTG showed fixed fetal heart rate (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of neuromuscular paramet...

  2. Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model.

    Directory of Open Access Journals (Sweden)

    Angèle Viola

    Full Text Available BACKGROUND: Rett syndrome (RS is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such as the Mecp2-deleted ("Mecp2-null" mouse have been employed to study neurological symptoms and brain function. However, an interdisciplinary approach drawing from chemistry, biology and neuroscience is needed to elucidate the mechanistic links between the genotype and phenotype of this genetic disorder. METHODOLOGY/PRINCIPAL FINDINGS: We performed, for the first time, a metabolomic study of brain extracts from Mecp2-null mice by using high-resolution magnetic resonance spectroscopy. A large number of individual water-soluble metabolites and phospholipids were quantified without prior selection for specific metabolic pathways. Results were interpreted in terms of Mecp2 gene deletion, brain cell function and brain morphology. This approach provided a "metabolic window" to brain characteristics in Mecp2-null mice (n = 4, revealing (i the first metabolic evidence of astrocyte involvement in RS (decreased levels of the astrocyte marker, myo-inositol, vs. wild-type mice; p = 0.034; (ii reduced choline phospholipid turnover in Mecp2-null vs. wild-type mice, implying a diminished potential of cells to grow, paralleled by globally reduced brain size and perturbed osmoregulation; (iii alterations of the platelet activating factor (PAF cycle in Mecp2-null mouse brains, where PAF is a bioactive lipid acting on neuronal growth, glutamate exocytosis and other processes; and (iv changes in glutamine/glutamate ratios (p = 0.034 in Mecp2-null mouse brains potentially indicating altered neurotransmitter recycling. CONCLUSIONS/SIGNIFICANCE: This study establishes, for the first time, detailed metabolic fingerprints of perturbed brain growth, osmoregulation and neurotransmission in a mouse model of Rett syndrome. Combined with morphological and neurological findings

  3. Brain perfusion SPECT and EEG findings in Rett syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lappalainen, R. [Children`s Castle Hospital, Dept. of Child Neurology, Helsinki (Finland); Liewendahl, K.; Nikkinen, P. [Univ. Central Hospital, Division of Nuclear Medicine, Laboratory Dept., Helsinki (Finland); Sainio, K.; Riikonen, R.S. [Univ. Central Hospital, Child Neurology, Helsinki (Finland)

    1997-01-01

    Thirteen patients (mean age 8.4 + 5.3 years) with Rett syndrome (RS) were studied with EEG and {sup 99m}Tc-HMPAO SPECT. Eleven patients had background abnormalities and 10 patients paroxysmal activity in EEG. Hypoperfusion of varying severity was detected in 11 patients, 7 patients having multiple lesions. Bifrontal hypoperfusion, observed in 6 patients, was the most distinctive finding. Hypoperfusion was observed also in other cortical regions, except for the occipital lobes. There was no correlation between severity of the background abnormality or presence of paroxysmal activity in EEG and grade of hypoperfusion. There was, however, an association between the severity of hypoperfusion and early manifestation of symptoms in patients with RS. Whether this early-onset group of patients represents a different disease entity or only reflects disease variability the basic pathology being the same, is a possibility that deserves further clarification. (au) 37 refs.

  4. Extensive authigenic quartz overgrowths in the gas-bearing Haynesville-Bossier Shale, USA

    Science.gov (United States)

    Dowey, Patrick J.; Taylor, Kevin G.

    2017-07-01

    In sandstone reservoirs, despite grain rearrangement during compaction, significant pore volumes may be retained prior to the onset of late diagenetic quartz cementation. In mudstone reservoirs, grain rearrangement during compaction results in significant pore volume reduction prior to late diagenesis. Where quartz overgrowths have been previously reported in post-compaction mudstones they have been in volumetrically low concentrations and interpreted as anomalous occurrences. Quartz cementation alters rock brittleness resulting in changes to mechanical fracture properties. Quartz overgrowths reduce reservoir porosity and permeability. We present petrographic evidence of two phases of quartz cement in the Haynesville-Bossier Shale: (i) grain replacive and (ii) quartz overgrowths. Carbonate grain replacement is volumetrically low (< 1%). Quartz overgrowths identified from SEM-CL imaging are volumetrically more significant (8-13%). Quartz overgrowths were most commonly observed in the sandy and coarse mudstone microfacies, but are present in both medium and fine mudstone microfacies. Petrographic evidence indicates three processes in the development of quartz overgrowths. Mica and pyrite are (i) engulfed and (ii) displaced by quartz overgrowth cement. The absence of a supportive, primary granular framework surrounding engulfed detrital and early authigenic minerals would indicate that quartz overgrowths are also (iii) replacive. Pressure dissolution of detrital quartz silt grains and smectite-to-illite transformation are likely sources of silica for quartz cement. This study is the first to document large-scale, replacive, authigenic quartz overgrowth development within a producing mudstone.

  5. Deep Brain Stimulation of the H Fields of Forel Alleviates Tics in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Clemens Neudorfer

    2017-06-01

    Full Text Available The current rationale for target selection in Tourette syndrome revolves around the notion of cortico-basal ganglia circuit involvement in the pathophysiology of the disease. However, despite extensive research, the ideal target for deep brain stimulation (DBS is still under debate, with many structures being neglected and underexplored. Based on clinical observations and taking into account the prevailing hypotheses of network processing in Tourette syndrome, we chose the fields of Forel, namely field H1, as a target for DBS. The fields of Forel constitute the main link between the striatopallidal system and the thalamocortical network, relaying pallidothalamic projections from core anatomical structures to the thalamic ventral nuclear group. In a retrospective study we investigated two patients suffering from chronic, medically intractable Tourette syndrome who underwent bilateral lead implantation in field H1 of Forel. Clinical scales revealed significant alleviation of tics and comorbid symptoms, namely depression and anxiety, in the postoperative course in both patients.

  6. Chronic pain and evoked responses in the brain: A magnetoencephalographic study in Complex Regional Pain Syndrome I and II

    NARCIS (Netherlands)

    Theuvenet, P.J.

    2012-01-01

    Complex Regional Pain Syndrome (CRPS) type I and II are chronic pain syndromes with comparable symptoms, only in CRPS II a peripheral nerve injury is present. No objective tests are currently available to differentiate the two types which hampers diagnosis and treatment. Non-invasive brain imaging

  7. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    DEFF Research Database (Denmark)

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders

    2016-01-01

    Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS...

  8. Brain MR Contribution to the Differential Diagnosis of Parkinsonian Syndromes: An Update

    Directory of Open Access Journals (Sweden)

    Giovanni Rizzo

    2016-01-01

    Full Text Available Brain magnetic resonance (MR represents a useful and feasible tool for the differential diagnosis of Parkinson’s disease. Conventional MR may reveal secondary forms of parkinsonism and may show peculiar brain alterations of atypical parkinsonian syndromes. Furthermore, advanced MR techniques, such as morphometric-volumetric analyses, diffusion-weighted imaging, diffusion tensor imaging, tractography, proton MR spectroscopy, and iron-content sensitive imaging, have been used to obtain quantitative parameters useful to increase the diagnostic accuracy. Currently, many MR studies have provided both qualitative and quantitative findings, reflecting the underlying neuropathological pattern of the different degenerative parkinsonian syndromes. Although the variability in the methods and results across the studies limits the conclusion about which technique is the best, specific radiologic phenotypes may be identified. Qualitative/quantitative MR changes in the substantia nigra do not discriminate between different parkinsonisms. In the absence of extranigral abnormalities, the diagnosis of PD is more probable, whereas basal ganglia changes (mainly in the putamen suggest the diagnosis of an atypical parkinsonian syndrome. In this context, changes in pons, middle cerebellar peduncles, and cerebellum suggest the diagnosis of MSA, in midbrain and superior cerebellar peduncles the diagnosis of PSP, and in whole cerebral hemispheres (mainly in frontoparietal cortex with asymmetric distribution the diagnosis of Corticobasal Syndrome.

  9. Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain Anomalies, Cardiomyopathy, and Severe Intellectual Disability

    Directory of Open Access Journals (Sweden)

    R. Curtis Rogers

    2011-01-01

    Full Text Available Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome. Methods. Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients' descriptions are compared with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings. Results. The patients reported here include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies, gyral abnormalities, seizures, hypotonia, and cardiomyopathy. Conclusion. Vici syndrome should be suspected in any child with agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous hypopigmentation.

  10. [Electrophysiological features (EEG) of ethanol withdrawal syndromes on isolated perfused rat brain].

    Science.gov (United States)

    Tezikov, E B; Litvicki, P F

    2015-01-01

    On isolated rat brains we studied native EEC and its derivates (mean EEC amplitude and power spectrums - Fourier transformation) during perfusion with ethanol (65 Mm/ L) and after its withdrawal. Previously rats were undergone ethanol burden for 6 days according to Majchrowicz procedures to get alcohol withdrawal syndrome. Duration perfusion without ethanol was 5, 10 and 20 min depending on the experimental schedule. Ethanol infusion between periods of withdrawal comprised 20 min. 55% of isolated brains shown epileptiform activity after 1-2 min of ethanol withdrawal but others manifested only increased mean amplitude and the power spectrums of EEC as well as an appearance of single or batch spikes. Differences between in vivo and in vitro conditions can be explained by the accelerated rate of ethanol elimination. The high positive correlation was obtained between EEC findings at the 5-th min of the first ethanol withdrawal and the same findings at the 5-th min of ethanol withdrawal in the second and the third episodes of ethanol withdrawal. Prolongation of withdrawal period more than 5th min caused brain death showing epileptiform activity. Isolated rat brain is the convenient subject to study pathogenesis of excitability of neurons and examination of drugs to treat alcohol withdrawal syndrome.

  11. Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes.

    Science.gov (United States)

    Motch Perrine, Susan M; Stecko, Tim; Neuberger, Thomas; Jabs, Ethylin W; Ryan, Timothy M; Richtsmeier, Joan T

    2017-01-01

    The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology. Using mouse models for craniosynostosis conditions, our group has precisely defined how unique craniosynostosis causing mutations in fibroblast growth factor receptors affect brain and skull morphology and dysgenesis involving coordinated tissue-specific effects of these mutations. Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2 S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases. Using linear distances estimated from three-dimensional coordinates of landmarks acquired from dual modality imaging of skull (high resolution micro-computed tomography and magnetic resonance microscopy) of mice at embryonic day 17.5, we confirm variation in brain and skull morphology in Fgfr2cC342Y/+ mice, Fgfr2+/S252W mice, and their unaffected littermates. Mutation-specific variation in neural and cranial tissue notwithstanding, patterns of integration of brain and skull differed only subtly between mice carrying either the FGFR2c C342Y or the FGFR2 S252W mutation and their unaffected littermates. However, statistically significant and substantial differences in morphological integration of brain and skull were revealed between the two mutant mouse models, each maintained on a different strain. Relative to the effects of

  12. Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes

    Directory of Open Access Journals (Sweden)

    Susan M. Motch Perrine

    2017-07-01

    Full Text Available The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology. Using mouse models for craniosynostosis conditions, our group has precisely defined how unique craniosynostosis causing mutations in fibroblast growth factor receptors affect brain and skull morphology and dysgenesis involving coordinated tissue-specific effects of these mutations. Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2 S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases. Using linear distances estimated from three-dimensional coordinates of landmarks acquired from dual modality imaging of skull (high resolution micro-computed tomography and magnetic resonance microscopy of mice at embryonic day 17.5, we confirm variation in brain and skull morphology in Fgfr2cC342Y/+ mice, Fgfr2+/S252W mice, and their unaffected littermates. Mutation-specific variation in neural and cranial tissue notwithstanding, patterns of integration of brain and skull differed only subtly between mice carrying either the FGFR2c C342Y or the FGFR2 S252W mutation and their unaffected littermates. However, statistically significant and substantial differences in morphological integration of brain and skull were revealed between the two mutant mouse models, each maintained on a different strain. Relative

  13. Interactive 3D visualization of structural changes in the brain of a person with corticobasal syndrome.

    Science.gov (United States)

    Hänel, Claudia; Pieperhoff, Peter; Hentschel, Bernd; Amunts, Katrin; Kuhlen, Torsten

    2014-01-01

    The visualization of the progression of brain tissue loss in neurodegenerative diseases like corticobasal syndrome (CBS) can provide not only information about the localization and distribution of the volume loss, but also helps to understand the course and the causes of this neurodegenerative disorder. The visualization of such medical imaging data is often based on 2D sections, because they show both internal and external structures in one image. Spatial information, however, is lost. 3D visualization of imaging data is capable to solve this problem, but it faces the difficulty that more internally located structures may be occluded by structures near the surface. Here, we present an application with two designs for the 3D visualization of the human brain to address these challenges. In the first design, brain anatomy is displayed semi-transparently; it is supplemented by an anatomical section and cortical areas for spatial orientation, and the volumetric data of volume loss. The second design is guided by the principle of importance-driven volume rendering: A direct line-of-sight to the relevant structures in the deeper parts of the brain is provided by cutting out a frustum-like piece of brain tissue. The application was developed to run in both, standard desktop environments and in immersive virtual reality environments with stereoscopic viewing for improving the depth perception. We conclude, that the presented application facilitates the perception of the extent of brain degeneration with respect to its localization and affected regions.

  14. Brief report: CANTAB performance and brain structure in pediatric patients with Asperger syndrome.

    Science.gov (United States)

    Kaufmann, Liane; Zotter, Sibylle; Pixner, Silvia; Starke, Marc; Haberlandt, Edda; Steinmayr-Gensluckner, Maria; Egger, Karl; Schocke, Michael; Weiss, Elisabeth M; Marksteiner, Josef

    2013-06-01

    By merging neuropsychological (CANTAB/cambridge neuropsychological test automated battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group differences regarding response speed on only one CANTAB subtest that is thought to tap fronto-executive network functions (SWM/spatial working memory). Across all participants, SWM performance was significantly associated with two brain regions (precentral gyrus white matter, precuneus grey matter), thus suggesting a close link between fronto-executive functions (SWM) and circumscribed fronto-parietal brain structures. Finally, symptom severity (ADOS total score) was best predicted by response speed on a set-shifting task (IES) thought to tap fronto-striatal functions (corrected R2 56%).

  15. Blood–brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome

    Science.gov (United States)

    Ivens, Sebastian; Gabriel, Szendro; Greenberg, George; Shelef, Ilan

    2013-01-01

    Cerebral hyperperfusion syndrome (CHS) may occur as a severe complication following surgical treatment of carotid stenosis. However, the mechanism inducing neurological symptoms in CHS remains unknown. We describe a patient with CHS presenting with seizures 24 h following carotid endarterectomy. Imaging demonstrated early ipsilateral blood–brain barrier (BBB) breakdown with electroencephalographic evidence of cortical dysfunction preceding brain edema. Using in vitro experiments on rat cortical tissue, we show that direct exposure of isolated brain slices to a serum-like medium induces spontaneous epileptiform activity, and that neuronal dysfunction is triggered by albumin. We propose BBB breakdown and subsequent albumin extravasation as a novel pathogenic mechanism underlying CHS and a potential target for therapy. PMID:20361293

  16. An allelopathy based model for the Listeria overgrowth phenomenon.

    Science.gov (United States)

    Fgaier, Hedia; Kalmokoff, Martin; Ells, Timothy; Eberl, Hermann J

    2014-01-01

    In a standard procedure of food safety testing, the presence of the pathogenic bacterium Listeria monocytogenes can be masked by non-pathogenic Listeria. This phenomenon of Listeria overgrowth is not well understood. We present a mathematical model for the growth of a mixed population of L. innocua and L. monocytogenes that includes competition for a common resource and allelopathic control of L. monocytogenes by L. innocua when this resource becomes limited, which has been suggested as one potential explanation for the overgrowth phenomenon. The model is tested quantitatively and qualitatively against experimental data in batch experiments. Our results indicate that the phenomenon of masked pathogens can depend on initial numbers of each population present, and on the intensity of the allelopathic effect. Prompted by the results for the batch setup, we also analyze the model in a hypothetical chemostat setup. Our results suggest that it might be possible to operate a continuous growth environment such that the pathogens outcompete the non-pathogenic species, even in cases where they would be overgrown in a batch environment. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Posterior reversible encephalopathy syndrome (PRES, an acute neurological syndrome due to reversible multifactorial brain edema: a case report

    Directory of Open Access Journals (Sweden)

    Camilla Cicognani

    2013-04-01

    Full Text Available Background: The essential features of Posterior Reversible Encephalopathy Syndrome (PRES are headache, mental changes, seizures, visual symptoms and often arterial hypertension. Brain RMN typically shows cortico-sottocortical parieto-occipital edema, with a bilateral and symmetric distribution. PRES develops in clinical conditions as hypertensive encephalopathy, preeclampsia/ eclampsia, autoimmune diseases, after transplantation, infections and as an adverse effect of immunosuppressive drugs or chemotherapy. It usually completely reverses with treatment, although permanent sequelae are possible in case of delayed or missed diagnosis. Case report: We describe the case of a transsexual (M!F and tetraplegic patient, admitted for neck and low back pain. She suddenly developed headache, confusion, seizures and severe hypertension with normal blood tests. RMN showed multiple cortico-sottocortical areas of vasogenic and citotoxic edema in temporo-occipital, parietal, frontal, and cerebellar regions. Soon after the beginning of the antihypertensive therapy, clinical recovery was observed, as well as the disappearance of edema at RMN. Discussion and conclusions: Although PRES is usually associated with definite pathological conditions, it is not always the case, as was for the patient here described, who had no predisposing factors in her past clinical history, and presented hypertension only in the acute phase of the syndrome. Since, moreover, PRES usually presents with acute non specific features and it can be misdiagnosed with other serious diseases, the clinician will be helped by the knowledge of this syndrome to promptly start diagnostic workup and treatments, and avoid permanent neurological deficits.

  18. Caught in the thickness of brain fog: exploring the cognitive symptoms of Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Anthony James Ocon

    2013-04-01

    Full Text Available Chronic Fatigue Syndrome (CFS is defined as greater than 6 months of persistent fatigue that is experienced physically and cognitively. The cognitive symptoms are generally thought to be a mild cognitive impairment, but individuals with CFS subjectively describe them as brain fog. The impairment is not fully understood and often is described as slow thinking, difficulty focusing, confusion, lack of concentration, forgetfulness, or a haziness in thought processes. Causes of brain fog and mild cognitive impairment have been investigated. Possible physiological correlates may be due to the effects of chronic orthostatic intolerance in the form of the Postural Tachycardia Syndrome and decreases in cerebral blood flow. In addition, fMRI studies suggest that individuals with CFS may require increased cortical and subcortical brain activation to complete difficult mental tasks. Furthermore, neurocognitive testing in CFS has demonstrated deficits in speed and efficiency of information processing, attention, concentration, and working memory. The cognitive impairments are then perceived as an exaggerated mental fatigue. As a whole, this is experienced by those with CFS as brain fog and may be viewed as the interaction of physiological, cognitive, and perceptual factors. Thus, the cognitive symptoms of CFS may be due to altered cerebral blood flow activation and regulation that are exacerbated by a stressor, such as orthostasis or a difficult mental task, resulting in the decreased ability to readily process information, which is then perceived as fatiguing and experienced as brain fog. Future research looks to further explore these interactions, how they produce cognitive impairments, and explain the perception of brain fog from a mechanistic standpoint.

  19. TGF-β1 gene polymorphism in renal transplant patients with and without gingival overgrowth.

    Science.gov (United States)

    Kozak, M; Kurzawski, M; Wajda, A; Lapczuk, J; Lipski, M; Dziewanowski, K; Drozdzik, M

    2011-05-01

    The incidence of gingival overgrowth among renal transplant patients treated with cyclosporine A ranges from 13% to 84.6%, and the overgrowth is not only esthetic but also a medical problem. We studied the determination of association between TGF-β1 (TGFB1) gene polymorphism and gingival overgrowth in kidney transplant patients medicated with cyclosporin A. Eighty-four kidney transplant patients with gingival overgrowth and 140 control transplant patients without overgrowth were enrolled into the case control study. TGFB1 polymorphism was determined using the PCR-RFLP assay for +869T > C in codon 10 and +915G > C in codon 25 as well as TaqMan real-time PCR assays for promoter -800G>A and -509C > T SNPs. In kidney transplant patients suffering from gingival overgrowth, mean score of gingival overgrowth was 1.38 ± 0.60, whereas in control subjects it was 0.0. The patients with gingival overgrowth were characterized by similar distribution of TGFB1 genotypes and allele in comparison to subjects without gingival overgrowth. Among 16 potentially possible haplotypes of TGFB1 gene, only four were observed in the studied sample of kidney transplant patients: G_C_T_G, G_T_C_G, G_C_C_C, and A_C_T_G, with similar frequency in patients with and without gingival overgrowth. No association between the TGFB1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporine A. © 2011 John Wiley & Sons A/S.

  20. Plasma from patients with HELLP syndrome increases blood-brain barrier permeability.

    Science.gov (United States)

    Wallace, Kedra; Tremble, Sarah M; Owens, Michelle Y; Morris, Rachael; Cipolla, Marilyn J

    2015-03-01

    Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood-brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor N(ω)-nitro-L-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction. © The Author(s) 2014.

  1. [Munchausen syndrome, a factitious injury, presenting brain abscess and intraventricular hemorrhage: a case report].

    Science.gov (United States)

    Goto, Yukihiro; Sasajima, Hiroyasu; Aita, Kazuyasu; Furuno, Yuichi; Owada, Kei; Tatsuzawa, Kazunori; Inoue, Yasuo; Mineura, Katsuyoshi

    2011-04-01

    Munchausen syndrome is a factitious disorder. Patients sometimes inflict injury on themselves in order to assume a sick role. The authors report a patient with Munchausen syndrome suffered from brain abscess, reopened wound and intraventricular hemorrhage. A 64-year-old male was admitted to our hospital after head injury. CT and MR imaging revealed a mass with surrounding edema in the right frontal lobe. The mass was surgically removed, and diagnosed as brain abscess. During the surgery, the authors noticed a small bone defect in the frontal bone above the brain abscess; therefore, we considered that head injury just concerned this lesion. There were no particular clues leading to other possible pathologies. After the first surgery, the patient presented atypical seizures several times. Once we discharged him from our hospital, we hospitalized him again because the wound had reopened. A subsequent operation was needed, and we removed the bone flap which we considered the origin of the infection. After the second surgery, he stabbed a nail into his head where the bone had been removed due to the previous surgery, and presented intraventricular hemorrhage. The hemorrhage decreased in size through non-surgical treatment and he was referred to the psychiatry department under a diagnosis of Munchausen syndrome. Diagnosis of this entity is difficult and often made at the later stage of hospitalization, because patients present a variety of complaints and clinical symptoms, which are hardly proved factitious. Early consideration of this syndrome will offer an early and accurate diagnosis, and is mandatory for a good prognosis.

  2. Overgrowth of the limbs: A prospective study of 21 Ghanaian patients

    African Journals Online (AJOL)

    Introduction: Overgrowth or gigantism is a congenital enlargement of the soft tissue parts of a limb often with associated enlargement of the skeleton, due to overgrowth of one or more cell types. It may be associated with lipofibromatosis, neurofibromatosis, hyperostosis, or hemihypertrophy. Extent of the burden is unknown ...

  3. Manifold decrease of sialic acid synthase in fetal Down syndrome brain.

    Science.gov (United States)

    Gulesserian, T; Engidawork, E; Fountoulakis, M; Lubec, G

    2007-01-01

    Down syndrome (DS, trisomy 21) is the most common genetic cause of mental retardation. A large series of biochemical defects have been observed in fetal and adult DS brain that help in unraveling the molecular mechanisms underlying mental retardation. As sialylation of glycoconjugates plays an important role in brain development, this study aimed to look at the sialic acid metabolism by measuring sialic acid synthase (SAS; N-acetylneuraminate synthase) in early second trimester fetal control and DS brain. In this regard, protein profiling was performed by two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization mass-spectrometry followed by database search and subsequent quantification of spot using specific software. SAS, the enzyme catalyzing synthesis of N-acetyl-neuraminic acid (syn: sialic acid) was represented as a single spot and found to be significantly and manifold reduced (P sialic acid metabolism, required for brain development and, more specifically, for sialylation of key brain proteins, including neuronal cell adhesion molecule and myelin associated glycoprotein.

  4. Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

    Science.gov (United States)

    Hotta, Jaakko; Saari, Jukka; Koskinen, Miika; Hlushchuk, Yevhen; Forss, Nina; Hari, Riitta

    2017-03-01

    Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q CRPS impairs action observation by affecting brain areas related to pain processing and motor control. This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Capgras Syndrome in a Patient with Parkinson's Disease after Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report.

    Science.gov (United States)

    Kyrtsos, Christina Rose; Stahl, Mark C; Eslinger, Paul; Subramanian, Thyagarajan; Lucassen, Elisabeth B

    2015-01-01

    Capgras syndrome is a delusional misidentification syndrome (DMS) which can be seen in neurodegenerative diseases such as Lewy body dementia and, to a lesser extent, in Parkinson's disease (PD). Here, we report the case of a 78-year-old man with a history of idiopathic PD who developed Capgras syndrome following bilateral subthalamic nucleus deep brain stimulation (DBS) implantation. As the risk of DMS has been related to deficits in executive, memory, and visuospatial function preoperatively, this case highlights the importance of continuing to improve patient selection for DBS surgery. Capgras syndrome is a rare potential complication of DBS surgery in PD patients with preexisting cognitive decline.

  6. Capgras Syndrome in a Patient with Parkinson's Disease after Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report

    Directory of Open Access Journals (Sweden)

    Christina Rose Kyrtsos

    2015-05-01

    Full Text Available Capgras syndrome is a delusional misidentification syndrome (DMS which can be seen in neurodegenerative diseases such as Lewy body dementia and, to a lesser extent, in Parkinson's disease (PD. Here, we report the case of a 78-year-old man with a history of idiopathic PD who developed Capgras syndrome following bilateral subthalamic nucleus deep brain stimulation (DBS implantation. As the risk of DMS has been related to deficits in executive, memory, and visuospatial function preoperatively, this case highlights the importance of continuing to improve patient selection for DBS surgery. Capgras syndrome is a rare potential complication of DBS surgery in PD patients with preexisting cognitive decline.

  7. Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Kalinowska, Magdalena; Castillo, Catherine; Francesconi, Anna

    2015-01-01

    Fragile X Syndrome, a leading cause of inherited intellectual disability and autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA-binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders.

  8. Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Magdalena Kalinowska

    Full Text Available Fragile X Syndrome, a leading cause of inherited intellectual disability and autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA-binding protein, Fragile X Mental Retardation Protein (FMRP. FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders.

  9. Balint's syndrome and post-acute brain injury rehabilitation: a case report.

    Science.gov (United States)

    Zgaljardic, Dennis J; Yancy, Sybil; Levinson, Jason; Morales, Gabrielle; Masel, Brent E

    2011-01-01

    Balint's syndrome includes the clinical symptom triad of simultagnosia, ocular apraxia and optic ataxia. These symptoms, in combination, are rare and can be quite debilitating as they impact visuospatial skills, visual scanning and attentional mechanisms. The literature addressing rehabilitation of individuals with Balint's syndrome is sparse. The current case report describes the outcome of a 58-year old male who presented with Balint's syndrome secondary to severe traumatic brain injury and following completion of a comprehensive post-acute brain injury rehabilitation programme. The patient was 4-months post-injury onset upon admission and received 6 months of rehabilitation services as an inpatient. The patient's comprehensive rehabilitation programme involved a 3-pronged approach including the implementation of (a) compensatory strategies, (b) remediation exercises and (c) transfer of learned skills in multiple environments and situations with implementation of psychoeducation and psychotherapy. Comprehensive neuropsychological and occupational therapy evaluations were performed at admission and at discharge in order to monitor cognitive, affective, neurological and functional change over time. Neuropsychological test improvements were noted on tasks that assess visuospatial functioning, although most gains were noted for functional and physical abilities.

  10. Incidence of amlodipine-induced gingival overgrowth in the rural population of Loni

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    Avneesh Tejnani

    2014-01-01

    Full Text Available Aims: Since the incidence of gingival overgrowth induced by amlodipine remains poorly defined, this study was carried out with an aim to determine the incidence. Materials and Methods: Dental patients who received amlodipine (N = 115, for more than 3 months were studied to determine the drug-induced gingival overgrowth. Clinical diagnosis of drug-induced overgrowth was verified by disappearance or decreased severity of gingival overgrowth after withdrawal of the causative drug. Results: The prevalence rate of amlodipine-induced gingival hyperplasia among experimental patients was 3.4%, while it was not observed among the control subjects. Oral examination revealed gingival overgrowth as a lobular or nodular enlargement on interdental papilla located in the anterior interproximal regions. Conclusions: In this study, there was a significant relationship between gingival inflammation resulting from dental plaque and drug dosage, and hyperplasia.

  11. Irritable Bowel Syndrome in female patients is associated with alterations in structural brain networks

    Science.gov (United States)

    Labus, Jennifer; Dinov, Ivo D.; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A.; Joshi, Shantanu; Thompson, Paul M.; Toga, Arthur W.; Mayer, Emeran A.

    2014-01-01

    Alterations in gray matter (GM) density/ volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with different chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at UCLA between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 Healthy Controls [HCs], 30± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between IBS and HC groups. Relative to HCs, the IBS group had lower volumes in bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found for the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for Early Trauma Inventory global score with the exception of the right amygdala and the left post central gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, the right cingulate gyrus and right thalamus were identified as significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. PMID:24076048

  12. Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge-Weber Syndrome.

    Science.gov (United States)

    Huang, Lan; Couto, Javier A; Pinto, Anna; Alexandrescu, Sanda; Madsen, Joseph R; Greene, Arin K; Sahin, Mustafa; Bischoff, Joyce

    2017-02-01

    Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain. Two human SWS brain specimens were fractionated by fluorescence-activated cell sorting into hematopoietic (CD45), endothelial (CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2), and perivascular (platelet-derived growth factor receptor beta) cells and cells negative for all markers. The sorted cell populations were analyzed for GNAQ p.R183Q mutation by droplet digital polymerase chain reaction. SWS patient-derived brain endothelial cells were selected by anti-CD31-coated magnetic beads and cultured in endothelial growth medium in vitro. The GNAQ p.R183Q mutation was present in brain endothelial cells in two SWS specimens, with mutant allelic frequencies of 34.7% and 24.0%. Cells negative for all markers also harbored the GNAQ mutation. The mutant allelic frequencies in these unidentified cells were 9.2% and 8.4%. SWS patient-derived brain endothelial cells with mutant allelic frequencies of 14.7% and 21% survived and proliferated in vitro. Our study provides evidence that GNAQ p.R183Q mutation is enriched in endothelial cells in SWS brain lesions and thereby reveals endothelial cells as a source of aberrant Gαq signaling. This will help to understand the pathophysiology of SWS, to discover biomarkers for predicting cerebral involvement, and to develop therapeutic targets to prevent neurological impairments in SWS. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

    Directory of Open Access Journals (Sweden)

    Akyol ES

    2015-03-01

    Full Text Available Esra Soydas Akyol,1 Yakup Albayrak,2 Murat Beyazyüz,3 Nurkan Aksoy,4 Murat Kuloglu,5 Kenji Hashimoto6 1Deparment of Psychiatry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 2Department of Psychiatry, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Psychiatry, Biga State Hospital, Çanakkale, Turkey; 4Department of Biochemistry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 5Department of Psychiatry, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 6Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background: Brain-derived neurotrophic factor (BDNF is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls.Methods: After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23 and nondeficit syndrome (N=35 according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels.Results: The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls.Conclusion: This study suggests that decreased BDNF levels may play a role in the pathophysio­logy of schizophrenic

  14. Proteus syndrome : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seon Young [Korea Veterans Hospital, Seoul (Korea, Republic of)

    1998-08-01

    Proteus syndrome is a rare congenital hamartomatous condition with a variety of abnormalities affecting all three germ layers including overgrowth of various parts of the body, hemihypertrophy, unusual skeletal malformation, skin lesions, and various tumors. I describe the radiologic findings in a 12 year-old boy with Proteus syndrome. Computed tomography and magnetic resonance imaging are very useful for the specific diagnosis.

  15. Beneficial effects of herbs, spices and medicinal plants on the metabolic syndrome, brain and cognitive function.

    Science.gov (United States)

    Panickar, Kiran S

    2013-03-01

    Herbs and spices have been used since ancient times to not only improve the flavor of edible food but also to prevent and treat chronic health maladies. While the scientific evidence for the use of such common herbs and medicinal plants then had been scarce or lacking, the beneficial effects observed from such use were generally encouraging. It is, therefore, not surprising that the tradition of using such herbs, perhaps even after the advent of modern medicine, has continued. More recently, due to an increased interest in understanding the nutritional effects of herbs/spices more comprehensively, several studies have examined the cellular and molecular modes of action of the active chemical components in herbs and their biological properties. Beneficial actions of herbs/spices include anti-inflammatory, antioxidant, anti-hypertensive, gluco-regulatory, and anti-thrombotic effects. One major component of herbs and spices is the polyphenols. Some of the aforementioned properties are attributed to the polyphenols and they are associated with attenuating the metabolic syndrome. Detrimental changes associated with the metabolic syndrome over time affect brain and cognitive function. Metabolic syndrome and type-2 diabetes are also risk factors for Alzheimer's disease and stroke. In addition, the neuroprotective effects of herbs and spices have been demonstrated and, whether directly or indirectly, such beneficial effects may also contribute to an improvement in cognitive function. This review evaluates the current evidence available for herbs/spices in potentially improving the metabolic syndrome, as well as their neuroprotective effects on the brain, and cognitive function in animal and human studies.

  16. Bilateral deep brain stimulation of the subthalamic nucleus in primary Meige syndrome.

    Science.gov (United States)

    Zhan, Shikun; Sun, Fafa; Pan, Yixin; Liu, Wei; Huang, Peng; Cao, Chunyan; Zhang, Jing; Li, Dianyou; Sun, Bomin

    2017-05-26

    OBJECTIVE Subthalamic nucleus deep brain stimulation has been shown to be effective in reducing symptoms of primary Meige syndrome. However, assessments of its efficacy and safety have been limited to several case reports and small studies. METHODS The authors performed a retrospective study to assess the efficacy and safety of bilateral subthalamic nucleus stimulation in 15 patients with primary Meige syndrome who responded poorly to medical treatments or botulinum toxin injections. Using the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Rating Scale, the authors evaluated the severity of patients' dystonia and related before surgery and at final follow-up during neurostimulation. The movement scale was assessed based on preoperative and postoperative video documentation by an independent rater who was unaware of each patient's neurostimulation status. Quality of life was assessed with the Medical Outcomes Study 36-Item Short-Form General Health Survey. RESULTS The dystonia movement subscores in 14 consecutive patients improved from 19.3 ± 7.6 (mean ± standard deviation) before surgery to 5.5 ± 4.5 at final follow-up (28.5 ± 16.5 months), with a mean improvement of 74% (p stimulation of the subthalamic nucleus immediately improved patient symptoms after stimulation and required lower stimulation parameters than those needed for pallidal deep brain stimulation for primary Meige syndrome. Four adverse events occurred in 3 patients; all of these events resolved without permanent sequelae. CONCLUSIONS These findings provide further evidence to support the long-term efficacy and safety of subthalamic nucleus stimulation as an alternative treatment for patients with medically intractable Meige syndrome.

  17. Neuropsychiatric Outcome of an Adolescent Who Received Deep Brain Stimulation for Tourette's Syndrome

    Directory of Open Access Journals (Sweden)

    S. J. Pullen

    2011-01-01

    Full Text Available This case study followed one adolescent patient who underwent bilateral deep brain stimulation of the centromedian parafascicular complex (CM-Pf for debilitating, treatment refractory Tourette's syndrome for a period of 1.5 years. Neurocognitive testing showed no significant changes between baseline and follow-up assessments. Psychiatric assessment revealed positive outcomes in overall adaptive functioning and reduction in psychotropic medication load in this patient. Furthermore, despite significant baseline psychiatric comorbidity, this patient reported no suicidal ideation following electrode implantation. Deep brain stimulation is increasingly being used in children and adolescents. This case reports on the positive neurologic and neuropsychiatric outcome of an adolescent male with bilateral CM-Pf stimulation.

  18. Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Baldermann, Juan Carlos; Schüller, Thomas; Huys, Daniel; Becker, Ingrid; Timmermann, Lars; Jessen, Frank; Visser-Vandewalle, Veerle; Kuhn, Jens

    2016-01-01

    A significant proportion of patients with Tourette syndrome (TS) continue to experience symptoms across adulthood that in severe cases fail to respond to standard therapies. For these cases, deep brain stimulation (DBS) is emerging as a promising treatment option. We conducted a systematic literature review to evaluate the efficacy of DBS for GTS. Individual data of case reports and series were pooled; the Yale Global Tic Severity Scale (YGTSS) was chosen as primary outcome parameter. In total, 57 studies were eligible, including 156 cases. Overall, DBS resulted in a significant improvement of 52.68% (IQR = 40.74, p brain targets resulted in comparable improvement rates, indicating a modulation of a common network. Future studies might focus on a better characterization of the clinical effects of distinct regions, rather than searching for a unique target. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Social brain development in williams syndrome: the current status and directions for future research.

    Science.gov (United States)

    Haas, Brian W; Reiss, Allan L

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental condition that occurs as a result of a contiguous deletion of ∼26-28 genes on chromosome 7q11.23. WS is often associated with a distinctive social phenotype characterized by an increased affinity toward processing faces, reduced sensitivity to fear related social stimuli and a reduced ability to form concrete social relationships. Understanding the biological mechanisms that underlie the social phenotype in WS may elucidate genetic and neural factors influencing the typical development of the social brain. In this article, we review available studies investigating the social phenotype of WS throughout development and neuroimaging studies investigating brain structure and function as related to social and emotional functioning in this condition. This review makes an important contribution by highlighting several neuro-behavioral mechanisms that may be a cause or a consequence of atypical social development in WS. In particular, we discuss how distinctive social behaviors in WS may be associated with alterations or delays in the cortical representation of faces, connectivity within the ventral stream, structure and function of the amygdala and how long- and short-range connections develop within the brain. We integrate research on typical brain development and from existing behavioral and neuroimaging research on WS. We conclude with a discussion of how genetic and environmental factors might interact to influence social brain development in WS and how future neuroimaging and behavioral research can further elucidate social brain development in WS. Lastly, we describe how ongoing studies may translate to improved social developmental outcomes for individuals with WS.

  20. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

    Directory of Open Access Journals (Sweden)

    Lino Becerra

    2014-01-01

    Full Text Available Pediatric complex regional pain syndrome (P-CRPS offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning. Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects. These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects.

  1. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

    Science.gov (United States)

    Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

    2014-01-01

    Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

  2. Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

    Science.gov (United States)

    Zebardast, Nazlee; Crowley, Michael J; Bloch, Michael H; Mayes, Linda C; Wyk, Brent Vander; Leckman, James F; Pelphrey, Kevin A; Swain, James E

    2013-10-30

    Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blocked-design fMRI paradigm. There were 33 participants: 17 with TS and 16 healthy individuals. As a measure of PPI-related brain activity, we looked for differential cerebral activation to prepulse-plus-pulse stimuli versus activation to pulse-alone stimuli. In healthy subjects, PPI was associated with increased activity in multiple brain regions, of which activation in the left middle frontal gyrus in the healthy controls showed a significant linear correlation with the degree of PPI measured outside of the magnet. Group comparisons identified nine regions where brain activity during PPI differed significantly between TS and healthy subjects. Among the TS subjects, activation in the left caudate was significantly correlated with current tic severity as measured by the total score on the Yale Global Tic Severity Scale. Differential activation of the caudate nucleus associated with current tic severity is consistent with neuropathological data and suggests that portions of cortical-striatal circuits may modulate the severity of tic symptoms in adulthood. © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Cardiotocographic and Doppler ultrasonographic findings in a fetus with brain death syndrome.

    Science.gov (United States)

    Chen, Yi-Ting; Hsu, Shih-Tien; Tseng, Jenn-Jhy; Chen, Wei-Chih; Ho, Esther Shih-Chu; Chou, Min-Min

    2006-09-01

    The diagnosis of brain death syndrome by cardiotocography (CTG) and Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation. A 23-year-old, gravida 2, para 0, woman was referred to our hospital because of the absence of fetal movements. CTG showed fixed fetal heart rate (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of neuromuscular parameters of biophysical profile (BPP) and the cessation of cerebral blood flow. Umbilical cord artery blood gas analysis showed pH 7.3, PaO2 30 mmHg and PaCO2 35 mmHg. A floppy male infant weighing 2,450 g was delivered vaginally at 36 weeks of gestation and the Apgar scores were 1 and 1 at 5 and 10 minutes, respectively. The neonate died 2 days after delivery. Postmortem examination of the brain showed diffuse, anoxic changes with multicystic encephalomalacia in both hemispheres and the brain stem. No other maternal or placental abnormalities were seen. The possibility of intrauterine brain death should be considered in all cases of prolonged fixed FHR pattern, accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness of this event may prevent unnecessary emergency cesarean section.

  4. [Mild traumatic brain injury and postconcussive syndrome: a re-emergent questioning].

    Science.gov (United States)

    Auxéméry, Y

    2012-09-01

    Blast injuries are psychologically and physically devastating. Notably, primary blast injury occurs as a direct effect of changes in atmospheric pressure caused by a blast wave. The combat-related traumatic brain injuries (TBI) resulting from exposure to explosions is highly prevalent among military personnel who have served in current wars. Traumatic brain injury is a common cause of neurological damage and disability among civilians and servicemen. Most patients with TBI suffer a mild traumatic brain injury with transient loss of consciousness. A controversial issue in the field of head injury is the outcome of concussion. Most individuals with such injuries are not admitted to emergency units and receive a variable degree of medical attention. Nevertheless, cranial traumas vary in their mechanisms (blast, fall, road accident, bullet-induced craniocerebral injury) and in their gravity (from minor to severe). The majority of subjects suffering concussion have been exposed to explosion or blast injuries, which have caused minor cranial trauma. Although some authors refuse to accept the reality of post-concussion syndrome (PCS) and confuse it with masked depression, somatic illnesses or post-traumatic stress, we have raised the question again of its existence, without denying the intricate links with other psychiatric or neurological disorders. Although the mortality rate is negligible, the traumatic sequel after mild traumatic brain injury is clear. A difference in initial somatic severity is noted between the serious somatic consequences of a severe cranial trauma compared with the apparently benign consequences of a minor cranial trauma. However, the long-term consequences of the two types of impacts are far from negligible: PCS is a source of morbidity. The prognosis for minor cranial traumas is benign at vital level but a number of patients will develop long-term complaints, which contrast with the negativity of the clinical examination and complementary

  5. A case of Baraitser-Winter syndrome with unusual brain MRI findings: pachygyria, subcortical-band heterotopia, and periventricular heterotopia.

    Science.gov (United States)

    Shiihara, Takashi; Maruyama, Ken-ichi; Yamada, Yoshiyuki; Nishimura, Akira; Matsumoto, Naomichi; Kato, Mitsuhiro; Sakazume, Satoru

    2010-06-01

    Baraitser-Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient's brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  6. Brain accumulation of myo-inositol in the trisomy 16 mouse, an animal model of Down's syndrome.

    OpenAIRE

    Shetty, H U; Holloway, H W; Acevedo, L D; Galdzicki, Z.

    1996-01-01

    myo-Inositol and several other polyols were measured in the tissues of the trisomy 16 mouse (animal model of Down's Syndrome; human trisomy 21) and diploid controls. myo-Inositol was found to be selectively elevated in the brain of the trisomy 16 mouse. However, peripheral tissues showed no elevation. These results are consistent with the cerebrospinal fluid and plasma data reported previously on myo-inositol in Down's Syndrome subjects.

  7. New Insights on Different Response of MDMA-Elicited Serotonin Syndrome to Systemic and Intracranial Administrations in the Rat Brain.

    Directory of Open Access Journals (Sweden)

    Ibrahim M Shokry

    Full Text Available In spite of the fact that systemic administration of MDMA elicits serotonin syndrome, direct intracranial administration fails to reproduce the effect. To reconcile these findings, it has been suggested that the cause of serotonin syndrome is attributed mainly to MDMA hepatic metabolites, and less likely to MDMA itself. Recently, however, this explanation has been challenged, and alternative hypotheses need to be explored. Here, we tested the hypothesis that serotonin syndrome is the result of excessive 5HT simultaneously in many brain areas, while MDMA administered intracranially fails to cause serotonin syndrome because it produces only a localized effect at the delivery site and not to other parts of the brain. This hypothesis was examined using adult male Sprague Dawley rats by comparing 5HT responses in the right and left hemispheric frontal cortices, right and left hemispheric diencephalons, and medullar raphe nucleus. Occurrence of serotonin syndrome was confirmed by measuring change in body temperature. Administration routes included intraperitoneal (IP, intracerebroventricular (ICV and reverse microdialysis. First, we found that IP administration caused excessive 5HT in all five sites investigated and induced hypothermia, suggesting the development of the serotonin syndrome. In contrast, ICV and reverse microdialysis caused excessive 5HT only in regions of delivery sites without changes in body-core temperature, suggesting the absence of the syndrome. Next, chemical dyes were used to trace differences in distribution and diffusion patterns between administration routes. After systemic administration, the dyes were found to be evenly distributed in the brain. However, the dyes administered through ICV or reverse microdialysis injection still remained in the delivery sites, poorly diffusing to the brain. In conclusion, intracranial MDMA administration in one area has no or little effect on other areas, which must be considered a plausible

  8. Blind Loop Syndrome

    Science.gov (United States)

    ... breeding ground for bacteria. The bacteria may produce toxins as well as block the absorption of nutrients. The greater the length of small bowel involved in the blind loop, the greater the chance of bacterial overgrowth. What triggers blind loop syndrome? Blind loop ...

  9. Brain Abscess and Keratoacanthoma Suggestive of Hyper IgE Syndrome

    Directory of Open Access Journals (Sweden)

    Soheyla Alyasin

    2015-01-01

    Full Text Available Hyper immunoglobulin-E (IgE syndrome is an autosomal immune deficiency disease. It is characterized by an increase in IgE and eosinophil count with both T-cell and B-cell malfunction. Here, we report an 8-year-old boy whose disease started with an unusual skin manifestation. When 6 months old he developed generalized red, nontender nodules and pathologic report of the skin lesion was unremarkable (inflammatory. Then he developed a painless, cold abscess. At the age of 4 years, he developed a seronegative polyarticular arthritis. Another skin biopsy was taken which was in favor of Keratoacanthoma. Laboratory workup for immune deficiency showed high eosinophil count and high level of immunoglobulin-E, due to some diagnostic criteria (NIH sores: 41 in 9-year-olds, he was suggestive of hyper IgE syndrome. At the age of 8, the patient developed an abscess in the left inguinal region. While in hospital, the patient developed generalized tonic colonic convulsion and fever. Brain computed tomography scan revealed an abscess in the right frontal lobe. Subsequently magnetic resonance imaging (MRI of the brain indicated expansion of the existing abscess to contralateral frontal lobe (left side. After evacuating the abscesses and administrating intravenous antibiotic, the patient’s condition improved dramatically and fever stopped.

  10. A microdeletion at 12q24.31 can mimic beckwith-wiedemann syndrome neonatally

    NARCIS (Netherlands)

    Baple, E.; Palmer, R.; Hennekam, R. C. M.

    2010-01-01

    We report on a patient who was initially suspected to have Beckwith-Wiedemann syndrome because of recurrent neonatal hypoglycaemias, macroglossia and overgrowth, but in whom no 11p15 abnormality could be found. Follow-up showed continued overgrowth and disturbed glucose homeostasis, a marked

  11. The dynamics of biofilm overgrowth of Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    E. A. Synetar

    2015-08-01

    Full Text Available The nature of microorganisms can exist in two physiological forms that allow microbes to preserve livelihoods and continue their life cycle. The first is the population of planktonic forms of microorganisms which live freely in the environment with the developed systems of active and passive mobility, contributing to the rapid spread of a liquid medium. The second forms are those expressing specific mechanisms of adhesion, and able to aggregate on biogenic and abiogenic surfaces. Even in the deep sea vast number of species of bacteria live in their inherent horizons. Thus, the study of biofilms tube life support systems, diagnostic, laparoscopic devices during prolonged catheterization of the urinary system is of great practical, theoretical and biological significance in medicine and biology. For almost 20% of catheter-associated infections antibiotic therapy is uneffective, particularly through the formation of microbial biofilms on the surface of urinary catheters. We characterized the dynamics of biofilm growth of Enterococcus faecalis on fragments ofsilicone catheter. The study was conducted using bacteriological and electron microscopic techniques. Study of the dynamics of biofilm formation was performed using E. faecalis strain 49, which is isolated from the urine of persons who are not the patients of the urological department of resuscitation and intensive therapy. Using scanning electron microscopy we have established dynamics and phase attachment ofE. faecalis bacteria and subsequent overgrowth of silicone catheter surface. Aftercalculations, index of adhesion on the turbulent wall amounted to 0,49 microbial cells. That is, every other cell of the monolayer adhered on the catheter. Area of biofilm growth of E. faecalis after 24 hour incubation was equal to 51.5 μm2, in 48 hours it increased to 231.5 μm2. After 72 hours of incubation we recorded the increase in biofilm growth of E. faecalisto 1922,8 μm2. The results were obtained

  12. Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

  13. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence.

    Science.gov (United States)

    Yau, Po Lai; Castro, Mary Grace; Tagani, Adrian; Tsui, Wai Hon; Convit, Antonio

    2012-10-01

    The prevalence of metabolic syndrome (MetS) parallels the rise in childhood obesity. MetS is associated with neurocognitive impairments in adults, but this is thought to be a long-term effect of poor metabolism. It would be important to ascertain whether these brain complications are also present among adolescents with MetS, a group without clinically manifest vascular disease and relatively short duration of poor metabolism. Forty-nine adolescents with and 62 without MetS, matched on age, socioeconomic status, school grade, gender, and ethnicity, received endocrine, MRI, and neuropsychological evaluations. Adolescents with MetS showed significantly lower arithmetic, spelling, attention, and mental flexibility and a trend for lower overall intelligence. They also had, in a MetS-dose-related fashion, smaller hippocampal volumes, increased brain cerebrospinal fluid, and reductions of microstructural integrity in major white matter tracts. We document lower cognitive performance and reductions in brain structural integrity among adolescents with MetS, thus suggesting that even relatively short-term impairments in metabolism, in the absence of clinically manifest vascular disease, may give rise to brain complications. In view of these alarming results, it is plausible that obesity-associated metabolic disease, short of type 2 diabetes mellitus, may be mechanistically linked to lower the academic and professional potential of adolescents. Although obesity may not be enough to stir clinicians or even parents into action, these results in adolescents strongly argue for an early and comprehensive intervention. We propose that brain function be introduced among the parameters that need to be evaluated when considering early treatment of childhood obesity.

  14. Brain structural alterations in obese children with and without Prader-Willi Syndrome.

    Science.gov (United States)

    Xu, Mingze; Zhang, Yi; von Deneen, Karen M; Zhu, Huaiqiu; Gao, Jia-Hong

    2017-08-01

    Prader-Willi syndrome (PWS) is a genetic imprinting disorder that is mainly characterized by hyperphagia and childhood obesity. Previous neuroimaging studies revealed that there is a significant difference in brain activation patterns between obese children with and without PWS. However, whether there are differences in the brain structure of obese children with and without PWS remains elusive. In the current study, we used T1-weighted and diffusion tensor magnetic resonance imaging to investigate alterations in the brain structure, such as the cortical volume and white matter integrity, in relation to this eating disorder in 12 children with PWS, 18 obese children without PWS (OB) and 18 healthy controls. Compared with the controls, both the PWS and OB groups exhibited alterations in cortical volume, with similar deficit patterns in 10 co-varying brain regions in the bilateral dorsolateral and medial prefrontal cortices, right anterior cingulate cortex, and bilateral temporal lobe. The white matter integrities of the above regions were then examined with an analysis method based on probabilistic tractography. The PWS group exhibited distinct changes in the reduced fractional anisotropy of white matter fibers connected to the co-varying regions, whereas the OB group did not. Our findings indicated that PWS and OB share similar gray matter alterations that are responsible for the development of eating disorders. Additionally, the distinct white matter alterations might explain the symptoms associated with food intake in PWS, including excessive hyperphagia and constant hunger. Hum Brain Mapp 38:4228-4238, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  16. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  17. Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome.

    Science.gov (United States)

    Shokouhi, Mahsa; Clarke, Collin; Morley-Forster, Patricia; Moulin, Dwight E; Davis, Karen D; St Lawrence, Keith

    2017-10-14

    Brain plasticity is demonstrated in complex regional pain syndrome (CRPS), although it is unclear how it modulates at different stages of CRPS. The observation that symptoms can progress over time suggests that the pattern of brain changes might also evolve. We measured structural and functional changes as well as sensorimotor integration at the early stage (ES) and late stage (LS) of CRPS. Twelve ES patients, 16 LS patients, and 16 age- and sex-matched controls were recruited. Gray matter (GM) volume was estimated using voxel-based morphometry. Cerebral perfusion was measured using arterial spin labeling, because it provides a measure of resting neural activity. Connectivity to sensorimotor regions was evaluated using blood-oxygen level-dependent images. The ES group showed reduced GM volume and perfusion in areas associated with spatial body perception, somatosensory cortex, and the limbic system, whereas the LS group exhibited increased perfusion in the motor cortex but no changes in GM volume. However, in the LS group, GM volume in areas associated with pain processing was negatively correlated with average pain levels, likely reflecting a response to ongoing pain. Furthermore, connectivity to sensorimotor cortex showed disruptions in regions associated with motor control and planning, implying impairment of higher-order motor control. This article presents brain changes at ES and LS of CRPS. We found different patterns of brain changes between these 2 stages. Understanding modulation of brain plasticity at different stages of CRPS could help understand the diversity in outcomes and treatment response and hopefully improve treatment planning. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

    Science.gov (United States)

    Segar, David J; Chodakiewitz, Yosef G; Torabi, Radmehr; Cosgrove, G Rees

    2015-06-01

    Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

  19. Effect of rehabilitation on a patient suffering from a tuberculous brain abscess with Gerstmann's syndrome: case report

    Directory of Open Access Journals (Sweden)

    Kuo CL

    2012-05-01

    Full Text Available Chih-Lan Kuo1, Sui-Foon Lo1,2, Chun-Lin Liu3, Chia-Hui Chou4, Li-Wei Chou1,2,5¹Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; ²School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan; 4Department of Infectious disease, China Medical University Hospital, Taichung, Taiwan; 5Department of Physical Therapy, China Medical University, Taichung, TaiwanAbstract: There are few reports in the literature of tuberculous brain abscess. Tuberculous brain abscess usually occurs in an immunocompromised host. Almost all previously documented cases have involved acquired immune deficiency syndrome. We encountered a 53-year-old right-handed immunocompetent male who was initially suspected of having a cerebrovascular accident due to acute-onset right hemiparesis and paresthesia. A tentative diagnosis of brain tumor versus brain abscess was made on imaging studies. The patient was finally diagnosed with a tuberculous brain abscess based upon deterioration on imaging and a positive tuberculosis culture. The tuberculous brain abscess was located in the left parietal lobe, which resulted in Gerstmann's syndrome and right-sided apraxia. Stereotactic surgery was performed. He was also given antituberculosis chemotherapy and comprehensive rehabilitation. Considerable improvement was noted after rehabilitation. The patient even returned to a normal life and work. Our case demonstrates that an aggressive intensive inpatient rehabilitation program combined with stereotactic surgery and effective antituberculosis therapy play an important role in improving the outcome for patients with tuberculous brain abscess, Gerstmann's syndrome, and right-sided apraxia.Keywords: tuberculous brain abscess, Gerstmann's syndrome, rehabilitation

  20. Neurobehavioral Consequences of HTLV-III Brain Infection and Acquired Immune Deficiency Syndrome (AIDS) Encephalopathy: A Prospective Study

    Science.gov (United States)

    1990-02-15

    hypothesized, the neuropsychological evaluation of these patients has been the most revealing. Ongoing analyses have shown a subtle cognitive dysfunction ...AD-A220 180 +++AAD-A22 0t Available Copy FUNDING NO.: 87PP7856 TITLE: Neurobehavioral Consequences of HTLV -III Brain Infection and Acquired Immune...TITLE (Include Securty Classifiat:on) Neurobehavioral Consequences of HTLV -1II Brain Infection and Acquired Immune Deficiency Syndrome (AIDS

  1. Brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome.

    Science.gov (United States)

    Tajerian, Maral; Leu, David; Zou, Yani; Sahbaie, Peyman; Li, Wenwu; Khan, Hamda; Hsu, Vivian; Kingery, Wade; Huang, Ting Ting; Becerra, Lino; Clark, J David

    2014-10-01

    Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions. The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

  2. Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

    Science.gov (United States)

    Joshi, U; van der Sluijs, J A; Teule, G J J; Pijpers, R

    2005-09-01

    Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

  3. Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology.

    Science.gov (United States)

    Tramutola, Antonella; Di Domenico, Fabio; Barone, Eugenio; Arena, Andrea; Giorgi, Alessandra; di Francesco, Laura; Schininà, Maria Eugenia; Coccia, Raffaella; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

    2017-03-01

    Among the putative mechanisms proposed to be common factors in Down syndrome (DS) and Alzheimer's disease (AD) neuropathology, deficits in protein quality control (PQC) have emerged as a unifying mechanism of neurodegeneration. Considering that disturbance of protein degradation systems is present in DS and that oxidized/misfolded proteins require polyubiquitinylation for degradation via the ubiquitin proteasome system, this study investigated if dysregulation of protein polyubiquitinylation is associated with AD neurodegeneration in DS. Postmortem brains from DS cases before and after development of AD neuropathology and age-matched controls were analyzed. By selectively isolating polyubiquitinated proteins, we were able to identify specific proteins with an altered pattern of polyubiquitinylation as a function of age. Interestingly, we found that oxidation is coupled with polyubiquitinylation for most proteins mainly involved in PQC and energy metabolism. This is the first study showing alteration of the polyubiquitinylation profile as a function of aging in DS brain compared with healthy controls. Understanding the onset of the altered ubiquitome profile in DS brain may contribute to identification of key molecular regulators of age-associated cognitive decline. Disturbance of the polyubiquitinylation machinery may be a key feature of aging and neurodegeneration. In DS, age-associated deficits of the proteolytic system may further exacerbate the accumulation of oxidized/misfolded/polyubiquitinated proteins, which is not efficiently degraded and may become harmful to neurons and contribute to AD neuropathology. Antioxid. Redox Signal. 26, 280-298.

  4. The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.

    Science.gov (United States)

    Milenkovic, I; Jarc, J; Dassler, E; Aronica, E; Iyer, A; Adle-Biassette, H; Scharrer, A; Reischer, T; Hainfellner, J A; Kovacs, G G

    2017-04-28

    Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life. We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well. Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD. © 2017 British Neuropathological Society.

  5. Surface properties and implantation site affect the capsular fibrotic overgrowth.

    Science.gov (United States)

    Bakeine, G J; Bertolotti, A; Latina, M; Congiu, T; Prati, U; Roveda, L; Trotta, F; Tormen, M; Fabrizio, E Di; Carlini, G; Facoetti, A; Nano, R

    2007-12-15

    Transplantation of encapsulated pancreatic islets is a promising approach for the treatment of type 1 diabetes. Large-scale application of this technique, however, is hampered by insufficient biocompatibility of the capsules. In this study, we have evaluated the biocompatibility of a new synthetic material with six different chemical groups on their surface (amino, carboxy-sulfate, carboxylate, hydroxylate, sulfate, and PMMA) used for the fabrication of the microcapsules. Eight Lewis rats were inoculated with a suspension of empty capsules made for each candidate material in the retroperitoneal ileopsoas muscle and renal subcapsular space. Four weeks later kidney and muscle containing the capsules were explanted, paraffin embedded, sectioned and stained with Sirius Red and Masson's Trichrome for histological analysis. The amount of fibrosis was also ultrastructurally evaluated with scanning electron microscopy. The samples were then subjected to digitalized quantitative analysis using specific software to determine the degree of fibrotic overgrowth. The quantification of collagen deposition, calculated in proximity of the microcapsules, was expressed as a percentage of the total area and can be considered a good index for the biocompatibility, an essential prerequisite for functional pancreatic islet transplantation. The results show that subcapsular renal space is the best implantation site and the positive surface charge induces a more intense collagen synthesis. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.

  6. [Bacterial overgrowth in small intestine in patients with liver cirrhosis].

    Science.gov (United States)

    Chesta, J; Silva, M; Thompson, L; del Canto, E; Defilippi, C

    1991-06-01

    Hepatic encephalopathy, bacterial infections and endotoxemia in cirrhotic patients have been related to colonic flora. However, an abnormal small bowel bacterial content could also be implied. We investigated small bowel bacterial overgrowth (SIBO) by jejunal cultures in 14 cirrhotic patients and 5 control subjects, and indirectly by the lactulose H2 breath test in 22 patients with cirrhosis and 12 controls. SIBO was demonstrated by cultures in 64% of cirrhotic patients and 1 of 5 controls. The breath test was positive for SIBO in 45% of patients with cirrhosis and 8% of controls. No differences were noted between patients with alcoholic and non-alcoholic liver disease. According to fasting H2 breath levels, SIBO was significantly correlated with the Child-Pugh score for hepatic function (r = 0.45; p < 0.05). Also, patients with positive criteria for SIBO in jejunal cultures had worse hepatic function in comparison to cirrhotics with normal jejunal bacterial counts (p < 0.05). Thus SIBO is frequent in patients with hepatic cirrhosis and is associated with impairment in hepatic function.

  7. Placental overgrowth in mice lacking the imprinted gene Ipl.

    Science.gov (United States)

    Frank, Dale; Fortino, Weiwei; Clark, Lorraine; Musalo, Raymond; Wang, Wenxian; Saxena, Anjana; Li, Chi-Ming; Reik, Wolf; Ludwig, Thomas; Tycko, Benjamin

    2002-05-28

    The Ipl (Tssc3) gene lies in an extended imprinted region of distal mouse chromosome 7, which also contains the Igf2 gene. Expression of Ipl is highest in placenta and yolk sac, where its mRNA is derived almost entirely from the maternal allele. Ipl encodes a small cytoplasmic protein with a pleckstrin-homology (PH) domain. We constructed two lines of mice with germ-line deletions of this gene (Ipl(neo) and Ipl(loxP)) and another line deleted for the similar but nonimprinted gene Tih1. All three lines were viable. There was consistent overgrowth of the Ipl-null placentas, with expansion of the spongiotrophoblast. These larger placentas did not confer a fetal growth advantage; fetal size was normal in Ipl nulls with the Ipl(neo) allele and was decreased slightly in nulls with the Ipl(loxP) allele. When bred into an Igf2 mutant background, the Ipl deletion partially rescued the placental but not fetal growth deficiency. Neither fetal nor placental growth was affected by deletion of Tih1. These results show a nonredundant function for Ipl in restraining placental growth. The data further indicate that Ipl can act, at least in part, independently of insulin-like growth factor-2 signaling. Thus, genomic imprinting regulates multiple pathways to control placental size.

  8. Atomically precise, coupled quantum dots fabricated by cleaved edge overgrowth

    Science.gov (United States)

    Wegscheider, W.; Schedelbeck, G.; Bichler, M.; Abstreiter, G.

    Recent progress in the fabrication of quantum dots by molecular beam epitaxy along three directions in space is reviewed. The optical properties of different sample structures consisting of individual quantum dots, pairs of coupled dots as well as of linear arrays of dots are studied by microscopic photoluminescence spectroscopy. The high degree of control over shape, composition and position of the 7×7×7 nm3 size GaAs quantum dots, which form at the intesection of three orthogonal quantum wells, allows a detailed investigation of the influence of coupling between almost identical zero-dimensional objects. In contrast to the inhomogeneously broadened quantum well and quantum wire signals originating from the complex twofold cleaved edge overgrowth structure, the photoluminescence spetrum of an individual quantum dot exhibits a single sharp line (full width at half maximum denomination "artificial atoms" for the quantum dots. It is further demonstrated that an "artifical molecule", characterized by the existence of bonding and antibonding states can be assembled from two of such "artificial atoms". The coupling strength between the "artificial atoms" is adjusted by the "interatomic" distance and is reflected in the energetic separation of the bonding and antibonding levels and the linewidths of the corresponding interband transitions.

  9. Chasing tics in the human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for tourette syndrome.

    Science.gov (United States)

    Almeida, Leonardo; Martinez-Ramirez, Daniel; Rossi, Peter J; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S

    2015-04-01

    Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.

  10. Can chlorhexidine mouthwash twice daily ameliorate cyclosporine-induced gingival overgrowth?

    Directory of Open Access Journals (Sweden)

    Ching-Hwa Gau

    2013-03-01

    Conclusion: These findings suggest that chlorhexidine mouthwash used twice daily may reduce the severity of CsA-induced gingival overgrowth. Further research is warranted to determine the optimal dose and treatment regimen.

  11. Reye Syndrome

    Science.gov (United States)

    Reye syndrome is a rare illness that can affect the blood, liver, and brain of someone who has recently ... a viral illness, seek medical attention immediately. Reye syndrome can lead to a coma and brain death, ...

  12. In vivo brain anatomy of adult males with Fragile X syndrome: an MRI study.

    LENUS (Irish Health Repository)

    Hallahan, Brian P

    2011-01-01

    Fragile X Syndrome (FraX) is caused by the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome, and is a leading cause of learning disability (mental retardation) worldwide. Relatively few studies, however, have examined the neuroanatomical abnormalities associated with FraX. Of those that are available many included mixed gender populations, combined FraX children and adults into one sample, and employed manual tracing techniques which measures bulk volume of particular regions. Hence, there is relatively little information on differences in grey and white matter content across whole brain. We employed magnetic resonance imaging to investigate brain anatomy in 17 adult males with FraX and 18 healthy controls that did not differ significantly in age. Data were analysed using stereology and VBM to compare (respectively) regional brain bulk volume, and localised grey\\/white matter content. Using stereology we found that FraX males had a significant increase in bulk volume bilaterally of the caudate nucleus and parietal lobes and of the right brainstem, but a significant decrease in volume of the left frontal lobe. Our complimentary VBM analysis revealed an increased volume of grey matter in fronto-striatal regions (including bilaterally in the caudate nucleus), and increased white matter in regions extending from the brainstem to the parahippocampal gyrus, and from the left cingulate cortex extending into the corpus callosum. People with FraX have regionally specific differences in brain anatomy from healthy controls with enlargement of the caudate nuclei that persists into adulthood.

  13. Intrinsic brain abnormalities in irritable bowel syndrome and effect of anxiety and depression.

    Science.gov (United States)

    Qi, Rongfeng; Liu, Chang; Ke, Jun; Xu, Qiang; Zhong, Jianhui; Wang, Fangyu; Zhang, Long Jiang; Lu, Guang Ming

    2016-12-01

    This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences. IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing.

  14. Deep brain stimulation for Tourette’s syndrome: the case for targeting the thalamic centromedian-parafascicular complex.

    Directory of Open Access Journals (Sweden)

    Paola Testini

    2016-11-01

    Full Text Available Tourette syndrome is a neurologic condition characterized by both motor and phonic tics and is typically associated with psychiatric comorbidities, including obsessive-compulsive disorder/behavior and attention deficit hyperactivity disorder and can be psychologically and socially debilitating. It is considered a disorder of the cortico-striato-thalamo-cortical circuitry, as suggested by pathophysiology studies and therapeutic options. Among these, deep brain stimulation of the centromedian-parafascicular nuclear complex (CM-Pf of the thalamus is emerging as a valuable treatment modality for patients affected by severe, treatment resistant TS. Here we review the most recent experimental evidence for the pivotal role of CM-Pf in the pathophysiology of Tourette syndrome, discuss potential mechanisms of action that may mediate the effects of CM-Pf deep brain stimulation in Tourette syndrome, and summarize its clinical efficacy.

  15. Bilateral deep brain stimulation of the nucleus accumbens for comorbid obsessive compulsive disorder and Tourette's syndrome.

    Science.gov (United States)

    Sachdev, Perminder Singh; Cannon, Elisabeth; Coyne, Terry J; Silburn, Peter

    2012-09-12

    We present the case of a 32-year-old Caucasian woman with severe treatment-refractory obsessive compulsive disorder (OCD) and Tourette's syndrome. Both conditions were present prior to age 5 and impacted significantly on the patient's functioning. Multiple trials of evidence-based pharmacological and behavioural therapies had not achieved remission of symptoms. Bilateral deep brain stimulation of the nucleus accumbens was undertaken to treat both illnesses but with a particular focus on OCD, as the patient identified this as the more debilitating of the two disorders. Following surgery there was an immediate improvement in OCD and tic severity. At follow-up 8 months later, there was a 90% improvement in OCD symptoms and a 57% improvement in tic severity. No intraoperative or postoperative complications or adverse events occurred and there were no undesired effects of stimulation.

  16. Functional brain asymmetry, attentional modulation, and interhemispheric transfer in boys with Tourette syndrome

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Lundervold, Arvid; Grüner, Renate

    2007-01-01

    on the right ear stimulus in the dichotic listening situation is thought to involve the same prefrontal attentional and executive functions that are involved in the suppression of tics, whereas, performance when focusing attention on the left ear stimulus additionally involves a callosal transfer...... to shift attention normally when instructed to focus on the right ear stimulus. When instructed to focus attention on the left ear stimulus, however, performance deteriorated in the TS group. Correlations with CC area further supported the hypothesized presence of deviant callosal functioning in the TS......We tested the hypothesis that children with Tourette syndrome (TS) would exhibit aberrant brain lateralization compared to a healthy control (HC) group in an attention-modulation version of a verbal dichotic listening task using consonant-vowel syllables. The modulation of attention to focus...

  17. [Retinal and brain infarctions secondary to acute carotid thrombosis in ovarian hyperstimulation syndrome].

    Science.gov (United States)

    Querol, L; Martínez-Corral, M; Martí, E; Martí-Fábregas, J

    2008-06-01

    Ovarian hyperstimulation syndrome (OHSS) is an uncommon but potentially life-threatening iatrogenic condition that may appear following ovulation induction in the course of some fertility treatments. This may lead to further complications, some of which may be severe, such as thromboembolic events. Though rarely, it can therefore be a potential cause of stroke. We report the case of a 34-year old woman under ovulation induction treatment who developed retinal and brain infarctions secondary to internal carotid occlusion. Oral anticoagulation was administered and recovery was good in spite of the persistence of carotid occlusion in follow-up magnetic ressonance imaging- angiographies. This is the first case of carotid occlusion following an OHSS reported in Spain and the eighth one published in the literature. Current literature on cerebrovascular complications in OHSS is also briefly reviewed.

  18. Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy

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    Jae Meen Lee

    2016-02-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS surgery in a cerebral palsy (CP patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

  19. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children

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    Jeffrey R. Donowitz

    2016-01-01

    Full Text Available Recent studies suggest small intestine bacterial overgrowth (SIBO is common among developing world children. SIBO’s pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO’s association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90 of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60 and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62. Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02 and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004 were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation.

  20. Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children

    Science.gov (United States)

    Haque, Rashidul; Kirkpatrick, Beth D.; Alam, Masud; Lu, Miao; Kabir, Mamun; Kakon, Shahria Hafiz; Islam, Bushra Zarin; Afreen, Sajia; Musa, Abu; Khan, Shaila Sharmeen; Colgate, E. Ross; Carmolli, Marya P.; Ma, Jennie Z.

    2016-01-01

    ABSTRACT Recent studies suggest small intestine bacterial overgrowth (SIBO) is common among developing world children. SIBO’s pathogenesis and effect in the developing world are unclear. Our objective was to determine the prevalence of SIBO in Bangladeshi children and its association with malnutrition. Secondary objectives included determination of SIBO’s association with sanitation, diarrheal disease, and environmental enteropathy. We performed a cross-sectional analysis of 90 Bangladeshi 2-year-olds monitored since birth from an impoverished neighborhood. SIBO was diagnosed via glucose hydrogen breath testing, with a cutoff of a 12-ppm increase over baseline used for SIBO positivity. Multivariable logistic regression was performed to investigate SIBO predictors. Differences in concomitant inflammation and permeability between SIBO-positive and -negative children were compared with multiple comparison adjustment. A total of 16.7% (15/90) of the children had SIBO. The strongest predictors of SIBO were decreased length-for-age Z score since birth (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 to 0.60) and an open sewer outside the home (OR, 4.78; 95% CI, 1.06 to 21.62). Recent or frequent diarrheal disease did not predict SIBO. The markers of intestinal inflammation fecal Reg 1β (116.8 versus 65.6 µg/ml; P = 0.02) and fecal calprotectin (1,834.6 versus 766.7 µg/g; P = 0.004) were elevated in SIBO-positive children. Measures of intestinal permeability and systemic inflammation did not differ between the groups. These findings suggest linear growth faltering and poor sanitation are associated with SIBO independently of recent or frequent diarrheal disease. SIBO is associated with intestinal inflammation but not increased permeability or systemic inflammation. PMID:26758185

  1. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

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    Sarah J Moum

    Full Text Available Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  2. Study habits among Nigerian secondary school students with brain fag syndrome

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    Olufemi Morakinyo

    2010-01-01

    Full Text Available Brain Fag Syndrome (BFS is a psychiatric disorder associated with study affecting two to four out of every ten African students. One of the consequences of this illness is early foreclosure of education in affected students. Etiological factors such as nervous predisposition, motivation for achievement, and psycho-stimulant use have been found associated with it. However, the contributions of study habits to the pathogenesis of this study-related illness deserve more attention than has been given. We carried out this cross-sectional study to ascertain the types of study habits associated with BFS among a sample of senior secondary school students in Ile-Ife, Nigeria. Five hundred students from six schools in Ile-Ife were selected using a stratified random sampling technique. The selected students completed the Socio-demographic Data Schedule, the Brain Fag Syndrome Scale, and Bakare’s Study Habit Inventory. The prevalence of BFS was 40.2% (201. There were no significant socio-demographic variables identifying BFS students apart from those without BFS. The significant measures of study habits that predicted BFS were homework and assignments, examinations, and written work. Those with BFS had 3.58 times the odds to perform poorly on homework and assignments, 3.27 times the odds to perform poorly on examinations, and 1.01 times the odds to perform poorly on written work compared to those without BFS. We concluded that the results of this study suggest that homework and assignments, examinations, and written work were significant study habit variables associated with BFS.

  3. Novel molecular pathways elicited by mutant FGFR2 may account for brain abnormalities in Apert syndrome.

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    Erika Yeh

    Full Text Available Apert syndrome (AS, the most severe form craniosynostosis, is characterized by premature fusion of coronal sutures. Approximately 70% of AS patients carry S252W gain-of-function mutation in FGFR2. Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS. Here, we hypothesized that S252W mutation leads not only to overstimulation of FGFR2 downstream pathway, but likewise induces novel pathological signaling. First, we profiled global gene expression of wild-type and S252W periosteal fibroblasts stimulated with FGF2 to activate FGFR2. The great majority (92% of the differentially expressed genes (DEGs were divergent between each group of cell populations and they were regulated by different transcription factors. We than compared gene expression profiles between AS and CS cell populations and did not observe correlations. Therefore, we show for the first time that S252W mutation in FGFR2 causes a unique cell response to FGF2 stimulation. Since our gene expression results suggested that novel signaling elicited by mutant FGFR2 might be associated with central nervous system (CNS development and maintenance, we next investigated if DEGs found in AS cells were also altered in the CNS of an AS mouse model. Strikingly, we validated Strc (stereocilin in newborn Fgfr2(S252W/+ mouse brain. Moreover, immunostaining experiments suggest a role for endothelial cells and cerebral vasculature in the establishment of characteristic CNS dysmorphologies in AS that has not been proposed by previous literature. Our approach thus led to the identification of new target genes directly or indirectly associated with FGFR2 which are contributing to the pathophysiology of AS.

  4. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

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    Satoshi eUmeda

    2015-03-01

    Full Text Available Postural tachycardia syndrome (PoTS, a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety and depression. Although the estimated prevalence of PoTS is approximately 5-10 times ascommon as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI with voxel-based morphometry (VBM applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL procedure to examine variation in regional brain structure associated with PoTS. We recruited eleven patients with established PoTS and twenty-three age-matched normal controls. Group comparison of grey matter volume revealed diminished grey matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation and increased vulnerability to psychiatric symptoms in PoTS patients.

  5. Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept.

    Science.gov (United States)

    Molina, Rene; Okun, Michael S; Shute, Jonathan B; Opri, Enrico; Rossi, P Justin; Martinez-Ramirez, Daniel; Foote, Kelly D; Gunduz, Aysegul

    2017-09-29

    Deep brain stimulation (DBS) has emerged as a promising intervention for the treatment of select movement and neuropsychiatric disorders. Current DBS therapies deliver electrical stimulation continuously and are not designed to adapt to a patient's symptoms. Continuous DBS can lead to rapid battery depletion, which necessitates frequent surgery for battery replacement. Next-generation neurostimulation devices can monitor neural signals from implanted DBS leads, where stimulation can be delivered responsively, moving the field of neuromodulation away from continuous paradigms. To this end, the authors designed and chronically implemented a responsive stimulation paradigm in a patient with medically refractory Tourette syndrome. The patient underwent implantation of a responsive neurostimulator, which is capable of responsive DBS, with bilateral leads in the centromedian-parafascicular (Cm-Pf) region of the thalamus. A spectral feature in the 5- to 15-Hz band was identified as the control signal. Clinical data collected prior to and after 12 months of responsive therapy revealed improvements from baseline scores in both Modified Rush Tic Rating Scale and Yale Global Tic Severity Scale scores (64% and 48% improvement, respectively). The effectiveness of responsive stimulation (p = 0.16) was statistically identical to that of scheduled duty cycle stimulation (p = 0.33; 2-sided Wilcoxon unpaired rank-sum t-test). Overall, responsive stimulation resulted in a 63.3% improvement in the neurostimulator's projected mean battery life. Herein, to their knowledge, the authors present the first proof of concept for responsive stimulation in a patient with Tourette syndrome.

  6. Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

    Science.gov (United States)

    Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

    2016-03-01

    Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome

    Science.gov (United States)

    Lindhurst, Marjorie J.; Sapp, Julie C.; Teer, Jamie K.; Johnston, Jennifer J.; Finn, Erin M.; Peters, Kathryn; Turner, Joyce; Cannons, Jennifer L.; Bick, David; Blakemore, Laurel; Blumhorst, Catherine; Brockmann, Knut; Calder, Peter; Cherman, Natasha; Deardorff, Matthew A.; Everman, David B.; Golas, Gretchen; Greenstein, Robert M.; Kato, B. Maya; Keppler-Noreuil, Kim M.; Kuznetsov, Sergei A.; Miyamoto, Richard T.; Newman, Kurt; Ng, David; O’Brien, Kevin; Rothenberg, Steven; Schwartzentruber, Douglas J.; Singhal, Virender; Tirabosco, Roberto; Upton, Joseph; Wientroub, Shlomo; Zackai, Elaine H.; Hoag, Kimberly; Whitewood-Neal, Tracey; Robey, Pamela G.; Schwartzberg, Pamela L.; Darling, Thomas N.; Tosi, Laura L.; Mullikin, James C.; Biesecker, Leslie G.

    2011-01-01

    BACKGROUND The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K–AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.) PMID:21793738

  8. Differential Diagnosis and Management of Incomplete Locked-In Syndrome after Traumatic Brain Injury

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    Lauren Surdyke

    2017-01-01

    Full Text Available Locked-in syndrome (LIS is a rare diagnosis in which patients present with quadriplegia, lower cranial nerve paralysis, and mutism. It is clinically difficult to differentiate from other similarly presenting diagnoses with no standard approach for assessing such poorly responsive patients. The purpose of this case is to highlight the clinical differential diagnosis process and outcomes of a patient with LIS during acute inpatient rehabilitation. A 32-year-old female was admitted following traumatic brain injury. She presented with quadriplegia and mutism but was awake and aroused based on eye gaze communication. The rehabilitation team was able to diagnose incomplete LIS based on knowledge of neuroanatomy and clinical reasoning. Establishing this diagnosis allowed for an individualized treatment plan that focused on communication, coping, family training, and discharge planning. The patient was ultimately able to discharge home with a single caregiver, improving her quality of life. Continued evidence highlights the benefits of intensive comprehensive therapy for those with acquired brain injury such as LIS, but access is still limited for those with a seemingly poor prognosis. Access to a multidisciplinary, specialized team provides opportunity for continued assessment and individualized treatment as the patient attains more medical stability, improving long-term management.

  9. A diagnosis model for early Tourette syndrome children based on brain structural network characteristics

    Science.gov (United States)

    Wen, Hongwei; Liu, Yue; Wang, Jieqiong; Zhang, Jishui; Peng, Yun; He, Huiguang

    2016-03-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by the presence of multiple motor and vocal tics. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of action. The aim of our work is to select topological characteristics of structural network which were most efficient for estimating the classification models to identify early TS children. Here we employed the diffusion tensor imaging (DTI) and deterministic tractography to construct the structural networks of 44 TS children and 48 age and gender matched healthy children. We calculated four different connection matrices (fiber number, mean FA, averaged fiber length weighted and binary matrices) and then applied graph theoretical methods to extract the regional nodal characteristics of structural network. For each weighted or binary network, nodal degree, nodal efficiency and nodal betweenness were selected as features. Support Vector Machine Recursive Feature Extraction (SVM-RFE) algorithm was used to estimate the best feature subset for classification. The accuracy of 88.26% evaluated by a nested cross validation was achieved on combing best feature subset of each network characteristic. The identified discriminative brain nodes mostly located in the basal ganglia and frontal cortico-cortical networks involved in TS children which was associated with tic severity. Our study holds promise for early identification and predicting prognosis of TS children.

  10. Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.

    Science.gov (United States)

    Tamás, Gertrúd; Kovács, Norbert; Varga, Noémi Ágnes; Barsi, Péter; Erőss, Loránd; Molnár, Mária Judit; Balás, István

    2016-01-01

    We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Interactive 3D visualization of structural changes in the brain of a person with corticobasal syndrome

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    Claudia eHänel

    2014-05-01

    Full Text Available The visualization of the progression of brain tissue loss, which occurs in neurodegenerative diseases like corticobasal syndrome (CBS, is an important prerequisite to understand the course and the causes of this neurodegenerative disorder. Common workflows for visual analysis are often based on single 2D sections since in 3D visualizations more internally situated structures may be occluded by structures near the surface. The reduction of dimensions from 3D to 2D allows for an holistic view onto internal and external structures, but results in a loss of spatial information. Here, we present an application with two 3D visualization designs to resolve these challenges. First, in addition to the volume changes, the semi-transparent anatomy is displayed with an anatomical section and cortical areas for spatial orientation. Second, the principle of importance-driven volume rendering is adapted to give an unrestricted line-of-sight to relevant structures by means of a frustum-like cutout. To strengthen the benefits of the 3D visualization, we decided to provide the application next to standard desktop environments in immersive virtual environments with stereoscopic viewing as well. This improves the depth perception in general and in particular for the second design. Thus, the application presented in this work allows for aneasily comprehensible visual analysis of the extent of brain degeneration and the corresponding affected regions.

  12. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

    Science.gov (United States)

    Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

    2016-02-01

    Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2015 John Wiley & Sons Ltd.

  13. Clinical research on intelligence seven needle therapy treated infants with brain damage syndrome.

    Science.gov (United States)

    Liu, Zhen-Huan; Li, Ye-Rong; Lu, Yong-Lin; Chen, Jie-Kui

    2016-06-01

    To assess whether the intelligence seven needle therapy administered in infants with perinatal brain damage syndrome (BDS) as early intervention would improve patients' neural development. A randomized controlled trial was conducted. Sixty-four infants with BDS were randomly assigned to two groups: the comprehensive group and the control group. Both groups received routine early intervention; in addition, the comprehensive group received intelligence seven needle therapy. Before and after treatment, the Bayley Scale of Infant Development (BSID), Gesell Developmental Schedules, Gross Motor Function Measure (GMFM), transcranial doppler ultrasound (TCD), and cranial imaging examination were tested for contrast. After treatment, the comprehensive group showed significant difference in the Mental Development Index (MDI) scores of BSID compared with the control group (P0.05) was observed. The children's development quotients (DQ) of the comprehensive group exhibited a significant superiority in improving the social adaptation DQ of Gesell Developmental Schedules compared with the control group (Plinguistic and social intercourse (P0.05). The total scores of GMFM in the comprehensive group were higher than those in the control group (Pintelligence, motion function, linguistic competence and social intercourse can be promoted for infants with perinatal BDS by treating with the intelligence seven needle therapy. This approach can improve the brain blood supply and promote the growth of frontal and parietal lobes.

  14. Visual Outcomes after Vitrectomy for Terson Syndrome Secondary to Traumatic Brain Injury.

    Science.gov (United States)

    Narayanan, Raja; Taylor, Stanford C; Nayaka, Ashraya; Deshpande, Riddhima; St Aubin, Daniel; Hrisomalos, Frank N; Hu, Jonathan; Rajagopal, Rithwick; Tewari, Asheesh; Apte, Rajendra S

    2017-01-01

    To evaluate visual outcomes after vitrectomy for intraocular hemorrhages secondary to traumatic brain injury. Retrospective, observational case series. A total of 28 eyes in 20 patients undergoing vitrectomy for Terson syndrome secondary to traumatic brain injury between 1997 and 2015. We reviewed the records of patients undergoing a standard 20-gauge or 23-gauge pars plana vitrectomy for intraocular hemorrhages secondary to traumatic brain injury, and the timing of vitrectomy in relation to the inciting intracranial event was recorded. The primary outcome measure was the change in the preoperative visual acuity score at postoperative month 1 and at the last noted clinic appointment. A total of 28 eyes in 20 patients (all male) underwent pars plana vitrectomy for intraocular hemorrhages secondary to traumatic brain injury. The mean preoperative baseline logarithm of the minimum angle of resolution (logMAR) (Snellen) best-corrected visual acuity (BCVA) was 1.81±0.56 (20/1290). At 1-month postoperative follow-up, the mean BCVA was 0.30±0.33 (20/40). At the date of the last follow-up, the mean BCVA was 0.15±0.24 (20/30) and the median BCVA was 0.00 (20/20). Although the difference between preoperative and postoperative BVCA was significantly different at 1 month and the final postoperative clinic visits (P < 0.001), there was not a correlation between preoperative visual acuity as a predictor of final postoperative visual acuity outcome (r=-0.32; P = 0.09; 95% confidence interval [CI] -0.62 - 0.06). At the date of the last follow-up, the differences in visual outcomes between the individuals undergoing vitrectomy within 3 months of the inciting event, 0.08±0.15 (20/25), were not significantly different than those undergoing surgical intervention after 3 months, 0.18±0.27 (20/30) (P = 0.28). Three cases among those undergoing vitrectomy after 3 months were complicated by retinal detachment, none of which resulted in a BCVA worse than when the patient originally

  15. Overgrowth of costochondral grafts in craniomaxillofacial reconstruction: Rare complication and literature review.

    Science.gov (United States)

    Yang, Shimao; Fan, Huanhuan; Du, Wen; Li, Jiayang; Hu, Jing; Luo, En

    2015-07-01

    Costochondral grafts (CCGs) have been used for the reconstruction of the craniomaxillofacial defects in various situations. However, there is controversy concerning the growth pattern of CCGs, which is often unpredictable and may manifest as overgrowth or no growth at all. This article summarizes the literature concerning overgrowth of CCGs in craniomaxillofacial reconstruction, and presents an uncommon case of treatment for overgrowth of costal graft in mandibular body reconstruction. The literature on overgrowth of CCGs in craniomaxillofacial reconstruction was reviewed with a chart. A 25-year-old man received mandibular partial resection because of adamantoblastoma, followed by replacement of costal graft. Two years postoperatively, he began to present with facial asymmetry and malocclusion. Clinical and radiologic image examination showed deviation of the chin to the left side, and overgrowth of the costal graft was diagnosed. Left sagittal split ramus osteotomy (SSRO), genioplasty, and left mandibular angle ostectomy (MAO) were performed. A total of 30 articles containing 68 cases of overgrowth of CCGs in craniomaxillofacial reconstructions have been reported since 1977, including the present case. During a 2-year follow-up, the patient's postoperative facial profile and contour appeared stable clinically and radiographically, and an improved symmetry facial contour and occlusion were achieved. The growth of CCGs may be influenced by complex factors such as the function of the mandible, inherent growth capacity, and possibly hormonal factors. Once overgrowth of the costal graft occurs in mandibular body reconstruction, SSRO combined with genioplasty and MAO could be the optimal option to restore a symmetrical face. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Molecular and Functional Characterization of Three Different Postzygotic Mutations in PIK3CA-Related Overgrowth Spectrum (PROS Patients: Effects on PI3K/AKT/mTOR Signaling and Sensitivity to PIK3 Inhibitors.

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    Daria C Loconte

    Full Text Available PIK3CA-related overgrowth spectrum (PROS include a group of disorders that affect only the terminal portion of a limb, such as type I macrodactyly, and conditions like fibroadipose overgrowth (FAO, megalencephaly-capillary malformation (MCAP syndrome, congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies (CLOVES syndrome and Hemihyperplasia Multiple Lipomatosis (HHML. Heterozygous postzygotic PIK3CA mutations are frequently identified in these syndromes, while timing and tissue specificity of the mutational event are likely responsible for the extreme phenotypic variability observed.We carried out a combination of Sanger sequencing and targeted deep sequencing of genes involved in the PI3K/AKT/mTOR pathway in three patients (1 MCAP and 2 FAO to identify causative mutations, and performed immunoblot analyses to assay the phosphorylation status of AKT and P70S6K in affected dermal fibroblasts. In addition, we evaluated their ability to grow in the absence of serum and their response to the PI3K inhibitors wortmannin and LY294002 in vitro.Our data indicate that patients' cells showed constitutive activation of the PI3K/Akt pathway. Of note, PI3K pharmacological blockade resulted in a significant reduction of the proliferation rate in culture, suggesting that inhibition of PI3K might prove beneficial in future therapies for PROS patients.

  17. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

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    Shashwath A Meda

    Full Text Available Williams syndrome (WS is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and

  18. Non-neuronal cell responses differ between normal and Down syndrome developing brains.

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    Kanaumi, Takeshi; Milenkovic, Ivan; Adle-Biassette, Homa; Aronica, Eleonora; Kovacs, Gabor G

    2013-12-01

    Down syndrome (DS), the most common genetic cause of mental retardation, is characterized by reduced number of neurons and delayed myelination. Though non-neuronal cells in the brain are vital for the development, survival, and function of neurons, there is a paucity of comparative studies of normal development and DS, in particular in the temporal lobe, a region of interest for cognitive decline. We evaluated immunoreactivity for CD68 (macrophage), HLA-DR (microglia), Olig2 and TPPP/p25 (oligodendroglia), and GFAP (astroglia) in the germinal matrix (GM), temporal lobe white matter (TeWM) and hippocampus from 14 weeks of gestations to newborn in 28 DS patients and 30 age-matched controls. The rate of increase of CD68 positive cells in the GM, CA1 hippocampal subregion and subiculum was significantly higher in DS. The density of Olig2 positive cells in the GM was lower in DS brains at early stages, then showed a transient increase contrasting controls. Olig2 expression increased more in the TeWM in DS, suggesting an altered pattern of oligodendrocyte progenitor generation. GFAP-immunoreactivity in DS was significantly lower in the middle pregnancy period in the TeWM and did not increase between early and middle periods in the GM compared to controls, likely reflecting a defect in astrocyte production. The altered expression of non-neuronal cell markers during normal development and DS may play a role in, or reflect, defective neurogenesis, leading to reduced number of neurons and delayed myelination in the developing DS brain. This has implications for the understanding of the mental retardation in DS patients. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  19. Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

    Science.gov (United States)

    Smeets, A Y J M; Duits, A A; Plantinga, B R; Leentjens, A F G; Oosterloo, M; Visser-Vandewalle, V; Temel, Y; Ackermans, L

    2016-03-01

    Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2±4.8 versus 12.8±3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0±2.0 versus 7.0±1.6, P=0.041) and in the total number of video-rated tics (259.6±107.3 versus 49.6±24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Resting-state EEG oscillatory dynamics in fragile X syndrome: abnormal functional connectivity and brain network organization.

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    Melle J W van der Molen

    Full Text Available Disruptions in functional connectivity and dysfunctional brain networks are considered to be a neurological hallmark of neurodevelopmental disorders. Despite the vast literature on functional brain connectivity in typical brain development, surprisingly few attempts have been made to characterize brain network integrity in neurodevelopmental disorders. Here we used resting-state EEG to characterize functional brain connectivity and brain network organization in eight males with fragile X syndrome (FXS and 12 healthy male controls. Functional connectivity was calculated based on the phase lag index (PLI, a non-linear synchronization index that is less sensitive to the effects of volume conduction. Brain network organization was assessed with graph theoretical analysis. A decrease in global functional connectivity was observed in FXS males for upper alpha and beta frequency bands. For theta oscillations, we found increased connectivity in long-range (fronto-posterior and short-range (frontal-frontal and posterior-posterior clusters. Graph theoretical analysis yielded evidence of increased path length in the theta band, suggesting that information transfer between brain regions is particularly impaired for theta oscillations in FXS. These findings are discussed in terms of aberrant maturation of neuronal oscillatory dynamics, resulting in an imbalance in excitatory and inhibitory neuronal circuit activity.

  1. Dendritic overgrowth and elevated ERK signaling during neonatal development in a mouse model of autism.

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    Ning Cheng

    Full Text Available Autism spectrum disorder (hereafter referred to as "ASD" is a heterogeneous neurodevelopmental condition characterized by impaired social communication and interactions, and restricted, repetitive activities or interests. Alterations in network connectivity and memory function are frequently observed in autism patients, often involving the hippocampus. However, specific changes during early brain development leading to disrupted functioning remain largely unclear. Here, we investigated the development of dendritic arbor of hippocampal CA1 pyramidal neurons in the BTBR T+tf/J (BTBR mouse model of autism. BTBR mice display the defining behavioural features of autism, and also exhibit impaired learning and memory. We found that compared to control C57BL/6J (B6 animals, the lengths of both apical and basal dendrites were significantly greater in neonatal BTBR animals. Further, basal dendrites in the BTBR mice had higher branching complexity. In contrast, cross-sectional area of the soma was unchanged. In addition, we observed a similar density of CA1 pyramidal neurons and thickness of the neuronal layer between the two strains. Thus, there was a specific, compartmentalized overgrowth of dendrites during early development in the BTBR animals. Biochemical analysis further showed that the extracellular signal-regulated kinases (ERK pathway was up-regulated in the hippocampus of neonatal BTBR animals. Since dendritic structure is critical for information integration and relay, our data suggest that altered development of dendrites could potentially contribute to impaired hippocampal function and behavior observed in the BTBR model, and that this might be related to increased activation of the ERK pathway.

  2. A partly-contacted epitaxial lateral overgrowth method applied to GaN material

    Science.gov (United States)

    Xiao, Ming; Zhang, Jincheng; Duan, Xiaoling; Shan, Hengsheng; Yu, Ting; Ning, Jing; Hao, Yue

    2016-04-01

    We have discussed a new crystal epitaxial lateral overgrowth (ELO) method, partly-contacted ELO (PC-ELO) method, of which the overgrowth layer partly-contacts with underlying seed layer. The passage also illustrates special mask structures with and without lithography and provides three essential conditions to achieve the PC-ELO method. What is remarkable in PC-ELO method is that the tilt angle of overgrowth stripes could be eliminated by contacting with seed layer. Moreover, we report an improved monolayer microsphere mask method without lithography of PC-ELO method, which was used to grow GaN. From the results of scanning electron microscopy, cathodoluminescence, x-ray diffraction (XRD), transmission electron microscopy, and atomic force microscope (AFM), overgrowth layer shows no tilt angle relative to the seed layer and high quality coalescence front (with average linear dislocation density <6.4 × 103 cm-1). Wing stripes peak splitting of the XRD rocking curve due to tilt is no longer detectable. After coalescence, surface steps of AFM show rare discontinuities due to the low misorientation of the overgrowth regions.

  3. TEM study of Pt-C replicas of calcite overgrowths precipitated from electrolyte solutions

    Science.gov (United States)

    Paquette, Jeanne; Vali, Hojatollah; Mucci, Alfonso

    1996-12-01

    The surface microtopography of synthetic magnesian calcite overgrowths on calcite powders was imaged on Pt-C replicas by transmission electron microscopy. The overgrowths were precipitated at room temperature under steady-state conditions from seawater-like solutions, in the presence and absence of Mg2+, SO42- and PO43- ions, and over a range of saturation states. Overgrowths produced from the Mg-free electrolyte show smooth coverage of the substrate with a few hillocks suggestive of spiral growth. Electrolytes containing Mg consistently produced patchy overgrowths on the {1014} faces of the seed crystals and differential inhibition of growth at their corners and edges. The patchy over-growths consist of flat-topped islands whose morphology is consistent with two-dimensional surface nucleation rather than spiral growth. The density of islands, their rounding, and their degree of coalescence increased with the saturation state of the precipitating solution. The effect of SO42- on the surface topography was imperceptible. Soluble reactive phosphate (SRP), on the other hand, clearly inhibited growth and dissolution along specific crystallographic directions. The development of irregular surfaces along specific edges and corners of the seed crystals shows that foreign ions promote the development of complex crystal morphology even at high saturation states.

  4. Epworth Sleepiness Scale- a novel tool to assess somnolence syndrome in patients receiving radiotherapy to the brain

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    Ritika Rajkumar Harjani

    2015-03-01

    Full Text Available Purpose: Radiation to brain causes early, early-delayed, and delayed side effects. There is paucity of literature regarding early-delayed effects like somnolence syndrome. Existing studies use general symptom assessment and visual analog scales. Epworth Sleepiness Scale (ESS is a time tested tool to assess daytime sleepiness in various conditions. In this study, the ESS has been used to determine the occurrence of somnolence in patients receiving cranial radiotherapy for primary and metastatic brain tumors. Thus the ESS has been used in a novel setting in our study. The ESS is a simple to administer questionnaire and may be useful in grading the severity of somnolence. To our knowledge, this is the second study to determine post radiation somnolence using ESS. Methods: This prospective study was conducted in 23 patients with primary and metastatic brain tumor. Patient demographics and tumor type and grade was noted. Those with Karnofsky Performance Scale (KPS less than 70 and with pre-existing sleep disorders were excluded. Radiotherapy regimen included palliative whole brain radiation for brain metastases and conformal adjuvant radiotherapy for primary brain tumors as per standard guidelines. All subjects included were administered ESS at baseline and weekly thereafter during and for 6 weeks after radiation. Results: All 23 patients (median age 50 years completed the planned questionnaires until 6 weeks post radiation. Twenty (87% patients had primary brain tumors whereas three (13% patients had metastatic lesions in brain. Of the 23 patients, 14 patients (60.86% had abnormal or increased daytime sleepiness; of which 3 had ESS scores greater than 16. Conclusion: Somnolence was noted in 60.86% of the patients, which is in accordance with existing literature. Epworth sleepiness scale is an effective tool to detect and quantify somnolence, However, it does not consider other symptoms of somnolence syndrome and hence should be combined with visual

  5. Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases

    NARCIS (Netherlands)

    Bour, L. J.; Ackermans, L.; Foncke, E. M. J.; Cath, D.; van der Linden, C.; Visser Vandewalle, V.; Tijssen, M. A.

    2015-01-01

    Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Event related potentials and event related

  6. Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases

    NARCIS (Netherlands)

    Bour, L.J.; Ackermans, L.; Foncke, E.M.J.; Cath, D.; van der Linden, C.; Vandewalle, V.V.; Tijssen, M.A.

    2015-01-01

    Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Methods: Event related potentials and

  7. Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome : Report of three cases

    NARCIS (Netherlands)

    Bour, L. J.; Ackermans, L.; Foncke, E. M. J.; Cath, D.; van der Linden, C.; Vandewalle, V. Visser; Tijssen, M. A.

    Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Methods: Event related potentials and

  8. Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain

    Science.gov (United States)

    Bailus, Barbara J; Pyles, Benjamin; McAlister, Michelle M; O'Geen, Henriette; Lockwood, Sarah H; Adams, Alexa N; Nguyen, Jennifer Trang T; Yu, Abigail; Berman, Robert F; Segal, David J

    2016-01-01

    Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS. However, widespread delivery of gene regulators to the brain remains challenging. Here, we report an engineered zinc finger-based artificial transcription factor (ATF) that, when injected i.p. or s.c., crossed the blood–brain barrier and increased Ube3a expression in the brain of an adult mouse model of AS. The factor displayed widespread distribution throughout the brain. Immunohistochemistry of both the hippocampus and cerebellum revealed an increase in Ube3a upon treatment. An ATF containing an alternative DNA-binding domain did not activate Ube3a. We believe this to be the first report of an injectable engineered zinc finger protein that can cause widespread activation of an endogenous gene in the brain. These observations have important implications for the study and treatment of AS and other neurological disorders. PMID:26727042

  9. Carotid ultrasonographic and brain computerized tomographic findings in patients with vascular ocular syndromes

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    Iwamoto, Toshihiko; Matsushima, Chikage; Shimizu, Souichirou; Takasaki, Masaru; Iwasaki, Takuya; Usui, Masahiko [Tokyo Medical Coll. (Japan)

    2002-02-01

    To clarify the characteristics of cerebrovascular lesions in subtypes of vascular ocular syndrome, including amaurosis fugax (AF), retinal artery occlusion (RAO), and retinal vein occlusion (RVO), 93 patients with vascular ocular syndrome were studied by means of carotid ultrasonography (US) and brain computerized tomography (CT). The subjects comprised 21 patients with AF, 37 with RAO, and 35 with RVO who were sequentially given these diagnoses by the department of ophthalmology. On the basis of US findings, carotid lesions were defined as the presence of plaque or stenotic changes. CT findings were assessed for the presence and distribution of low-density areas (LDAs). Mean age was similar in each group, ranging from 64.5 to 67.4 years. The RAO group had high rates of men, hypertension, and smokers. US showed that the prevalence of carotid lesions ipsilateral to the affected eye was high in the RAO group and that severe stenosis and ulcerated plaque were present in 28.6% of the AF group and 45.9% of the RAO group. On CT examination, cerebral infarctions appeared as LDAs in about 10% of the patients in each group, and the incidence and distribution of LDAs were similar. Of 13 patients with cerebral infarction, only 2 were presumably due to carotid lesions; the others had a variety of causes. The discrepancy between US and CT findings was attributed to the small number of patients with cerebral infarction, since most patients had visual defects as an initial symptom. Our results suggest that extracranial carotid lesions, considered to be a major risk factor for stroke, should be carefully assessed in patients with AF or RAO to prevent further stroke. (author)

  10. Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis.

    Science.gov (United States)

    Lee, Mi Ji; Cha, Jihoon; Choi, Hyun Ah; Woo, Sook-Young; Kim, Seonwoo; Wang, Shuu-Jiun; Chung, Chin-Sang

    2017-03-01

    Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood-brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology-based diagnosis of RCVS. We prospectively recruited 72 consecutive patients with thunderclap headache who did not have aneurysmal subarachnoid hemorrhage from April 2015 to July 2016 at the Samsung Medical Center. Based on the International Classification of Headache Disorders-3 beta criteria and neuroimaging, patients were classified as having RCVS (n = 41; "definite" in 29 imaging-proven patients and "probable" in 12 imaging-negative patients), other secondary causes (n = 7), and thunderclap headache of undetermined cause (n = 24). BBB breakdown was evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. BBB breakdown was documented in 20 (69.0%) patients with definite RCVS, 3 (25.0%) patients with probable RCVS, and none with other secondary causes. BBB breakdown was present in RCVS patients with (n = 4) and without (n = 19) concomitant posterior reversible encephalopathy syndrome. In patients with RCVS, the extent of BBB breakdown was independently associated with neurological complications (multivariate odds ratio = 1.48 per 1 territorial increase, 95% confidence interval = 1.04-2.12, adjusted p = 0.032). Three (12.5%) patients with thunderclap headache of undetermined cause were newly classified as having RCVS by the presence of BBB breakdown. This is the first study to show BBB breakdown in patients with RCVS. This finding might broaden our understanding of the pathophysiology and clinical spectrum of RCVS. Ann Neurol 2017;81:454-466. © 2017 American Neurological Association.

  11. Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model.

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    Khristofor Agassandian

    Full Text Available Bardet-Biedl syndrome (BBS is a genetically heterogeneous inherited human disorder displaying a pleotropic phenotype. Many of the symptoms characterized in the human disease have been reproduced in animal models carrying deletions or knock-in mutations of genes causal for the disorder. Thinning of the cerebral cortex, enlargement of the lateral and third ventricles, and structural changes in cilia are among the pathologies documented in these animal models. Ciliopathy is of particular interest in light of recent studies that have implicated primary neuronal cilia (PNC in neuronal signal transduction. In the present investigation, we tested the hypothesis that areas of the brain responsible for learning and memory formation would differentially exhibit PNC abnormalities in animals carrying a deletion of the Bbs4 gene (Bbs4-/-. Immunohistochemical localization of adenylyl cyclase-III (ACIII, a marker restricted to PNC, revealed dramatic alterations in PNC morphology and a statistically significant reduction in number of immunopositive cilia in the hippocampus and amygdala of Bbs4-/- mice compared to wild type (WT littermates. Western blot analysis confirmed the decrease of ACIII levels in the hippocampus and amygdala of Bbs4-/- mice, and electron microscopy demonstrated pathological alterations of PNC in the hippocampus and amygdala. Importantly, no neuronal loss was found within the subregions of amygdala and hippocampus sampled in Bbs4-/- mice and there were no statistically significant alterations of ACIII immunopositive cilia in other areas of the brain not known to contribute to the BBS phenotype. Considered with data documenting a role of cilia in signal transduction these findings support the conclusion that alterations in cilia structure or neurochemical phenotypes may contribute to the cognitive deficits observed in the Bbs4-/- mouse mode.

  12. [CLIPPERS syndrome with atypical distribution of lesions in magnetic resonance imaging of the brain].

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    Canneti, Beatrice; Mosqueira, Antonio J; Gilo, Francisco; Carreras, Teresa; Barbosa, Antonio; Meca-Lallana, Virginia; Vivancos, José

    2013-10-16

    CLIPPERS syndrome (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory process of the central nervous system whose distinguishing features are the enhancing punctiform lesions in the brainstem that appear in the magnetic resonance images. Clinically, it is accompanied by dysarthria, ataxia and diplopia, and usually responds to treatment with corticoids. Pathologically, T lymphocytes appear infiltrated in the perivascular spaces of the brainstem. We report the case of a 40-year-old woman with an initial subacute clinical picture of binocular diplopia, ataxia and dysarthria. The magnetic resonance brain scan revealed T2 hyperintense punctiform lesions in the stem, cerebellum, diencephalons and cortico-subcortical areas of both hemispheres, which were enhanced with contrast. An aetiological study was performed to rule out any underlying infectious, neoplastic or inflammatory origin, the results being negative. The patient was treated on two occasions with methylprednisolone, with a gradual lowering of the dosage, the response being favourable. Diplopia and ataxia, as in our case, are practically always present. The MR findings consist of punctiform enhancing lesions located in the pons extending towards the cerebellum, basal ganglia and corpus callosum, the enhancement gradient becoming lower as the distance increases rostrally away from the cortex, and caudally towards the spinal cord. In the case of our patient, this gradient is not respected, and the density found was similar to that of lesions at the supratentorial level. The differential diagnosis is wide-ranging and justifies an extensive diagnostic study with, in certain cases, a biopsy study of brain tissue. The disease courses in a relapsing-remitting pattern and the earlier steroid therapy is established and the more prolonged it is, the better the prognosis will be.

  13. Microstructural brain injury in post-concussion syndrome after minor head injury

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    Smits, Marion; Wielopolski, Piotr A.; Vernooij, Meike W.; Lugt, Aad van der [Erasmus MC-University Medical Centre Rotterdam, Department of Radiology (Hs-224), PO Box 2040, Rotterdam (Netherlands); Houston, Gavin C. [Applied Science Lab, GE Healthcare, Hertogenbosch (Netherlands); Dippel, Diederik W.J.; Koudstaal, Peter J. [Erasmus MC-University Medical Centre Rotterdam, Department of Neurology, Rotterdam (Netherlands); Hunink, M.G.M. [Erasmus MC-University Medical Centre Rotterdam, Department of Radiology (Hs-224), PO Box 2040, Rotterdam (Netherlands); Erasmus MC-University Medical Centre Rotterdam, Department of Epidemiology, Rotterdam (Netherlands); Harvard School of Public Health, Department of Health Policy and Management, Boston, MA (United States)

    2011-08-15

    After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages. Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images. Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only. The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome. (orig.)

  14. A novel gingival overgrowth mouse model induced by the combination of CsA and ligature-induced inflammation.

    Science.gov (United States)

    Okanobu, Ai; Matsuda, Shinji; Kajiya, Mikihito; Fujita, Tsuyoshi; Kittaka, Mizuho; Shiba, Hideki; Kurihara, Hidemi

    2017-06-01

    Drug-induced gingival overgrowth (DIGO) is a side effect of the enlargement of gingival tissue by phenytoin, nifedipine, and cyclosporine A (CsA). Gingival inflammation has been identified as a key factor that initiates DIGO. However, a sufficient animal model for clarifying the role of inflammation in DIGO has not yet been generated. We herein describe a novel CsA-induced gingival overgrowth mouse model to evaluate the role of inflammation. A ligature was placed around the second molar in maxillae for 7days to induce gingival inflammation, and CsA (50mg/kg/day) was administered to mice during each experimental period. The severity of gingival overgrowth and mRNA expression of inflammatory cytokines in gingiva were assessed by the gingival overgrowth degree, histological analyses, and RT-PCR. The administration of CsA for 28days in combination with ligation significantly increased the gingival overgrowth degree and expanded the connective tissue area. Increases in the gingival overgrowth degree continued in a time-dependent manner until 21days. Furthermore, the cessation of CsA reduced gingival overgrowth. Thin ligatures (7-0 size) induced weaker tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 mRNA expression and less gingival overgrowth than thick ligatures (5-0 ligature). Moreover, the administration of an antibiotic cocktail, which suppressed the expression of these inflammatory cytokines in gingiva, attenuated gingival overgrowth induced by ligatures and CsA. These results suggest that inflammation in gingival tissue plays a role in initiating CsA-induced gingival overgrowth. This gingival overgrowth mouse model has potential for elucidating the etiology of DIGO from the view point of gingival inflammation. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Image Analysis with the Brain Easy Analysis Tool (BEAT) Method in Cases of Encephalomalacia Following Shaken Baby Syndrome

    OpenAIRE

    George, Imataka; Yoshiyuki, Watabe; Keiko, Tsukada; Shigeko, Kuwashima; Teisuke, Hashimoto; Osamu, Arisaka; Department of Radiology, Dokkyo Medical University School of Medicine; Department of Pediatrics, Dokkyo Medical University School of Medicine

    2010-01-01

    Brain easy analysis tool( BEAT) is newly released software to calculate composite images both MRI andSPECT on computer graphics. At first, we herein report two cases with shaken baby syndrome associatedwith multicystic encephalomalasia diagnosed based on MRI. Next, we created fusion MRI-SPECT imagesusing BEAT. The result of composited images was not only well recognized in anatomical visually but alsoeasy to explain data to patients. This report is the second case report with this software ca...

  16. Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions

    OpenAIRE

    Hyland, Niall P; Quigley, Eamonn MM; Brint, Elizabeth

    2014-01-01

    Irritable bowel syndrome (IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as t...

  17. The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules.

    Science.gov (United States)

    King, A; Sandler, S; Andersson, A

    2001-12-05

    Microencapsulation of islets of Langerhans in alginate/poly-L-lysine (PLL)/alginate capsules may provide a method for transplantation in the absence of immunosuppression. The aim of this study was to investigate the problem of overgrowth on implanted capsules with regard to the composition of the capsules and host factors such as cytokine and nitric oxide production. Empty capsules were implanted to C57BL/6 mice for 1, 3, 7, or 28 days. Glucose oxidation rates showed the metabolic activity of the cellular overgrowth on retrieved capsules. DNA content, histological score, and retrieval rates were also measured to assess the overgrowth. It was noted that the pericapsular host reaction arose by day 7 and had not increased further by day 28. Capsules of varying alginate compositions and different concentrations of PLL were implanted for 7 days to either C57BL/6 or Balb/c mice. Capsules were also implanted to mice lacking the inducible nitric oxide synthase enzyme. Glucose oxidation rates, DNA content, and histological score were positively correlated to each other and negatively correlated to retrieval rates. The pericapsular reaction was reduced if PLL was omitted from the capsule or if a high mannuronic acid alginate was used. Balb/c mice had reduced cellular overgrowth on implanted capsules and had reduced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha in their peritoneal macrophages. The capsular overgrowth seemed more severe in animals lacking inducible nitric oxide synthase compared with wild-type controls. It is concluded that alginate composition, PLL, and recipient factors such as nitric oxide production and cytokine expression affect the cellular overgrowth on implanted alginate capsules. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 57: 374-383, 2001

  18. Marfan syndrome

    Directory of Open Access Journals (Sweden)

    T Sivasankari

    2017-01-01

    Full Text Available Marfan syndrome (MFS is the autosomal dominant-inherited multisystem connective-tissue disorder, with a reported incidence of 1 in 10,000 individuals and equal distribution in both genders. The main clinical manifestation of this disorder consists of an exaggerated length of the upper and lower limbs, hyperlaxity, scoliosis, alterations in the cardiovascular and pulmonary systems, and atypical bone overgrowth. Orofacial manifestations such as high-arched palate, hypodontia, long narrow teeth, bifid uvula, mandibular prognathism, and temporomandibular disorders are also common. Early diagnosis of MFS is essential to prevent the cardiovascular complications and treatment of orofacial manifestations, thus to increase the quality of life of the patient.

  19. Using saliva nitrite and nitrate levels as a biomarker for drug induced gingival overgrowth

    Directory of Open Access Journals (Sweden)

    Erkan eSukuroglu

    2015-12-01

    Full Text Available Aim: Drug-induced gingival overgrowth has a multifactorial nature and the pathogenesis is still uncertain. It has been suggested that Nitric Oxide (NO might play a role in the pathogenesis of drug-induced gingival overgrowth due to the contribution of NO to immune response and matrix degradation. NO levels in biological fluids have been used as a diagnostic biomarker in many diseases. The aim of this study is to determine whether NO levels in plasma, saliva and gingival crevicular fluid (GCF can serve as a potential biomarker for the evaluation of drug-induced gingival overgrowth risk. Material and Methods: A total of 104 patients, receiving cyclosporine A (n=35, phenytoin (n=25, nifedipine (n=26 or diltiazem (n=18 participated in the study. The amount of gingival overgrowth was evaluated with two indices and was given as percentage. Periodontal clinical parameters including plaque index (PI, gingival index (GI, gingival bleeding time index (GBTI and probing depth (PD were also assessed. Saliva, GCF and plasma samples were obtained from each participants. Nitrite and nitrate levels in saliva, GCF and plasma were analyzed by Griess reagent. Results: Salivary nitrite and nitrate levels in responders were significantly higher than those in non-responders in only phenytoin group (p˂0.05. Nitrite and nitrate levels of gingival crevicular fluid and plasma did not significantly differ between responders and non-responders in all study groups (p˃0.05. Salivary nitrite levels exhibited a significant correlation with PD, GBTI, severity of gingival overgrowth (%GO and GCF volume (p˂0.05. Additionally, a strong positive correlation was detected between saliva and plasma nitrate levels (p˂0.005. However, both nitrite and nitrate levels in GCF and plasma demonstrated no significant correlation with clinical parameters, GO severity and GCF volume (p˃0.05.Conclusion: Salivary nitrite and nitrate levels could be used as periodontal disease biomarkers in

  20. Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

    Science.gov (United States)

    Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

    2016-04-01

    Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Soluble (Prorenin Receptor and Obstructive Sleep Apnea Syndrome: Oxidative Stress in Brain?

    Directory of Open Access Journals (Sweden)

    Kazuhiro Takahashi

    2017-06-01

    Full Text Available (Prorenin receptor ((PRR is a multi-functional molecule that is related to both the renin-angiotensin system (RAS and vacuolar H+-ATPase (v-ATPase, an ATP-dependent multi-subunit proton pump. Soluble (PRR (s(PRR, which consists of the extracellular domain of (PRR, is present in blood and urine. Elevated plasma s(PRR concentrations are reported in patients with chronic kidney disease and pregnant women with hypertension or diabetes mellitus. In addition, we have shown that plasma s(PRR concentrations are elevated in patients with obstructive sleep apnea syndrome (OSAS. Interestingly, the levels are elevated in parallel with the severity of OSAS, but are not related to the presence of hypertension or the status of the circulating RAS in OSAS. It is known that v-ATPase activity protects cells from endogenous oxidative stress, and loss of v-ATPase activity results in chronic oxidative stress. We hypothesize that hypoxia and subsequent oxidative stress, perhaps in the brain, may be one of the factors that elevate plasma s(PRR levels in OSAS.

  2. Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.

    Science.gov (United States)

    Olmos-Serrano, Jose Luis; Kang, Hyo Jung; Tyler, William A; Silbereis, John C; Cheng, Feng; Zhu, Ying; Pletikos, Mihovil; Jankovic-Rapan, Lucija; Cramer, Nathan P; Galdzicki, Zygmunt; Goodliffe, Joseph; Peters, Alan; Sethares, Claire; Delalle, Ivana; Golden, Jeffrey A; Haydar, Tarik F; Sestan, Nenad

    2016-03-16

    Trisomy 21, or Down syndrome (DS), is the most common genetic cause of developmental delay and intellectual disability. To gain insight into the underlying molecular and cellular pathogenesis, we conducted a multi-region transcriptome analysis of DS and euploid control brains spanning from mid-fetal development to adulthood. We found genome-wide alterations in the expression of a large number of genes, many of which exhibited temporal and spatial specificity and were associated with distinct biological processes. In particular, we uncovered co-dysregulation of genes associated with oligodendrocyte differentiation and myelination that were validated via cross-species comparison to Ts65Dn trisomy mice. Furthermore, we show that hypomyelination present in Ts65Dn mice is in part due to cell-autonomous effects of trisomy on oligodendrocyte differentiation and results in slower neocortical action potential transmission. Together, these results identify defects in white matter development and function in DS, and they provide a transcriptional framework for further investigating DS neuropathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Deep brain stimulation in Gilles de la Tourette syndrome: killing several birds with one stone?

    Science.gov (United States)

    Hartmann, Andreas

    2016-01-01

    In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction. PMID:27746910

  4. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  5. Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome

    Science.gov (United States)

    Agren-Wilsson, A; Eklund, A; Koskinen, L; Bergenheim, A; Malm, J

    2005-01-01

    Background: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. Objective: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. Methods: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0–7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral PtiO2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. Results: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (pintracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS. PMID:16024885

  6. Early environmental therapy rescues brain development in a mouse model of Down syndrome.

    Science.gov (United States)

    Begenisic, Tatjana; Sansevero, Gabriele; Baroncelli, Laura; Cioni, Giovanni; Sale, Alessandro

    2015-10-01

    Down syndrome (DS), the most common genetic disorder associated with intellectual disabilities, is an untreatable condition characterized by a number of developmental defects and permanent deficits in the adulthood. Ts65Dn mice, the major animal model for DS, display severe cognitive and synaptic plasticity defects closely resembling the human phenotype. Here, we employed a multidisciplinary approach to investigate, for the first time in developing Ts65Dn mice, the effects elicited by early environmental enrichment (EE) on brain maturation and function. We report that exposure to EE resulted in a robust increase in maternal care levels displayed by Ts65Dn mothers and led to a normalization of declarative memory abilities and hippocampal plasticity in trisomic offspring. The positive effects of EE on Ts65Dn phenotype were not limited to the cognitive domain, but also included a rescue of visual system maturation. The beneficial EE effects were accompanied by increased BDNF and correction of over-expression of the GABA vesicular transporter vGAT. These findings highlight the beneficial impact of early environmental stimuli and their potential for application in the treatment of major functional deficits in children with DS. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Brain-computer interface with language model-EEG fusion for locked-in syndrome

    Science.gov (United States)

    Oken, Barry S.; Orhan, Umut; Roark, Brian; Erdogmus, Deniz; Fowler, Andrew; Mooney, Aimee; Peters, Betts; Miller, Meghan; Fried-Oken, Melanie B.

    2013-01-01

    Background Some non-invasive brain computer interface (BCI) systems are currently available for locked-in syndrome (LIS) but none have incorporated a statistical language model during text generation. Objective To begin to address the communication needs of individuals with LIS using a non-invasive BCI that involves Rapid Serial Visual Presentation (RSVP) of symbols and a unique classifier with EEG and language model fusion. Methods The RSVP Keyboard™ was developed with several unique features. Individual letters are presented at 2.5 per sec. Computer classification of letters as targets or non-targets based on EEG is performed using machine learning that incorporates a language model for letter prediction via Bayesian fusion enabling targets to be presented only 1–4 times. Nine participants with LIS and nine healthy controls were enrolled. After screening, subjects first calibrated the system, and then completed a series of balanced word generation mastery tasks that were designed with five incremental levels of difficulty, that increased by selecting phrases for which the utility of the language model decreased naturally. Results Six participants with LIS and nine controls completed the experiment. All LIS participants successfully mastered spelling at level one and one subject achieved level five. Six of nine control participants achieved level five. Conclusions Individuals who have incomplete LIS may benefit from an EEG-based BCI system, which relies on EEG classification and a statistical language model. Steps to further improve the system are discussed. PMID:24370570

  8. Brain-computer interface with language model-electroencephalography fusion for locked-in syndrome.

    Science.gov (United States)

    Oken, Barry S; Orhan, Umut; Roark, Brian; Erdogmus, Deniz; Fowler, Andrew; Mooney, Aimee; Peters, Betts; Miller, Meghan; Fried-Oken, Melanie B

    2014-05-01

    Some noninvasive brain-computer interface (BCI) systems are currently available for locked-in syndrome (LIS) but none have incorporated a statistical language model during text generation. To begin to address the communication needs of individuals with LIS using a noninvasive BCI that involves rapid serial visual presentation (RSVP) of symbols and a unique classifier with electroencephalography (EEG) and language model fusion. The RSVP Keyboard was developed with several unique features. Individual letters are presented at 2.5 per second. Computer classification of letters as targets or nontargets based on EEG is performed using machine learning that incorporates a language model for letter prediction via Bayesian fusion enabling targets to be presented only 1 to 4 times. Nine participants with LIS and 9 healthy controls were enrolled. After screening, subjects first calibrated the system, and then completed a series of balanced word generation mastery tasks that were designed with 5 incremental levels of difficulty, which increased by selecting phrases for which the utility of the language model decreased naturally. Six participants with LIS and 9 controls completed the experiment. All LIS participants successfully mastered spelling at level 1 and one subject achieved level 5. Six of 9 control participants achieved level 5. Individuals who have incomplete LIS may benefit from an EEG-based BCI system, which relies on EEG classification and a statistical language model. Steps to further improve the system are discussed.

  9. Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

    Directory of Open Access Journals (Sweden)

    Lefebvre Nicolas

    2007-05-01

    Full Text Available Background Hypersentivity Syndrome (HS may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature. Case presentation A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months. Conclusion Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.

  10. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis.

    Science.gov (United States)

    Tsang, S W; Auyeung, K K W; Bian, Z X; Ko, J K S

    2016-01-01

    Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients.

  11. Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial.

    Science.gov (United States)

    Welter, Marie-Laure; Houeto, Jean-Luc; Thobois, Stéphane; Bataille, Benoit; Guenot, Marc; Worbe, Yulia; Hartmann, Andreas; Czernecki, Virginie; Bardinet, Eric; Yelnik, Jerome; du Montcel, Sophie Tezenas; Agid, Yves; Vidailhet, Marie; Cornu, Philippe; Tanguy, Audrey; Ansquer, Solène; Jaafari, Nematollah; Poulet, Emmanuel; Serra, Giulia; Burbaud, Pierre; Cuny, Emmanuel; Aouizerate, Bruno; Pollak, Pierre; Chabardes, Stephan; Polosan, Mircea; Borg, Michel; Fontaine, Denys; Giordana, Bruno; Raoul, Sylvie; Rouaud, Tiphaine; Sauvaget, Anne; Jalenques, Isabelle; Karachi, Carine; Mallet, Luc

    2017-08-01

    Deep brain stimulation (DBS) has been proposed to treat patients with severe Tourette's syndrome, and open-label trials and two small double-blind trials have tested DBS of the posterior and the anterior internal globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS for severe Tourette's syndrome. In this randomised, double-blind, controlled trial, we recruited patients aged 18-60 years with severe and medically refractory Tourette's syndrome from eight hospitals specialised in movement disorders in France. Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS; 3 months later they were randomly assigned (1:1 ratio with a block size of eight; computer-generated pairwise randomisation according to order of enrolment) to receive either active or sham stimulation for the subsequent 3 months in a double-blind fashion. All patients then received open-label active stimulation for the subsequent 6 months. Patients and clinicians assessing outcomes were masked to treatment allocation; an unmasked clinician was responsible for stimulation parameter programming, with intensity set below the side-effect threshold. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) score between the beginning and end of the 3 month double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all randomly allocated patients who received active or sham stimulation during the double-blind period. We assessed safety in all patients who were enrolled and received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov, number NCT00478842. Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We randomly assigned 17 (89%) patients, with 16 completing blinded assessments (seven [44%] in the active stimulation group and nine [56%] in the sham stimulation group). We noted no significant difference in YGTSS score change between the beginning and the end of the 3 month double-blind period

  12. SacB-SacR gene cassette as the negative selection marker to suppress Agrobacterium overgrowth in Agrobacterium-mediated plant transformation

    Science.gov (United States)

    Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transformation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce ...

  13. Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions

    DEFF Research Database (Denmark)

    Schiffrin, E.J.; Parlesak, Alexandr; Bode, C.

    2009-01-01

    A study was conducted in healthy elderly living independently in senior housing to assess the impact of a probiotic yoghurt supplement on small intestinal bacterial overgrowth. Twenty-three participants with positive and thirteen participants with negative hydrogen breath test were studied before...

  14. Analysis of proliferative activity in oral gingival epithelium in immunosuppressive medication induced gingival overgrowth

    Directory of Open Access Journals (Sweden)

    Özdemir B Handan

    2006-05-01

    Full Text Available Abstract Background Drug-induced gingival overgrowth is a frequent adverse effect associated principally with administration of the immunosuppressive drug cyclosporin A and also certain antiepileptic and antihypertensive drugs. It is characterized by a marked increase in the thickness of the epithelial layer and accumulation of excessive amounts of connective tissue. The mechanism by which the drugs cause gingival overgrowth is not yet understood. The purpose of this study was to compare proliferative activity of normal human gingiva and in cyclosporine A-induced gingival overgrowth. Methods Gingival samples were collected from 12 generally healthy individuals and 22 Cyclosporin A-medicated renal transplant recipients. Expression of proliferating cell nuclear antigen was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and a monoclonal antibody for this antigen. Results There were differences between the Cyclosporin A group and control group in regard to proliferating cell nuclear antigen and epithelial thickness. In addition, the degree of stromal inflammation was higher in the Cyclosporin A group when compared with the control group. Conclusion The results suggest that the increased epithelial thickness observed in Cyclosporin A-induced gingival overgrowth is associated with increased proliferative activity in keratinocytes.

  15. Localized Pd Overgrowth on Cubic Pt Nanocrystals for Enhanced Electrocatalytic Oxidation of Formic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H.; Habas, S.E.; Somorjai, G.A.; Yang, P.

    2008-03-20

    Binary Pt/Pd nanoparticles were synthesized by localized overgrowth of Pd on cubic Pt seeds for the investigation of electrocatalytic formic acid oxidation. The binary particles exhibited much less self-poisoning and a lower activation energy relative to Pt nanocubes, consistent with the single crystal study.

  16. [Breath hydrogen test to evaluate lactose absorption and small bowel bacterial overgrowth in children].

    Science.gov (United States)

    dos Reis, J C; de Morais, M B; Fagundes Neto, U

    1999-01-01

    The aim of this study was to determine the lactose absorption capacity and possible existence of bacterial overgrowth in the small bowel in asymptomatic school children of low social economic level in Marilia, a city located in the interior of São Paulo state. Eighty three children aging 7 to 15 years old without any gastrointestinal manifestations at least 30 days prior to the tests were studied. All the patients had fasted for at least 8 hours before the tests were performed. Lactose absorption was evaluated by breath hidrogen test after an overload of lactose 18 g in 10% aquous solution. Lactose intolerance was determined by the occurrence of clinical symptoms, such as diarrhea, abdominal pain, flatulence, etc in the following 24 hours after the test was performed. Bacterial overgrowth was evaluated by the breath hidrogen test after a 10 g lactulose load in aqueous solution. Lactose malabsorption was detected in 19 (22.9%) children and lactose intolerance was observed in 10 (12%) children. Lactose intolerance was more frequently observed in children who showed lactose malabsorption (6/19; 31.6%) than in those who presented a normal test (4/64; 6.3%) (P = 0.008). Bacterial overgrowth was detected in six (7.2%) children and showed no statistical relationship with lactose malabsorption. Ontogenetic lactose malabsorption verified in this group of school children is similar to the reported for Caucasian populations. Presence of bacterial overgrowth confirms the existence of asymptomatic environmental enteropathy in children of low social economic level.

  17. An unusual case report of gingival overgrowth associated with the use of leflunomide

    Directory of Open Access Journals (Sweden)

    Ferdi Yavuz

    2016-04-01

    Full Text Available Leflunomide is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. Leflunomide induced side effects are hepatotoxicity, immunosuppression, skin reactions, peripheral neuropathy, hypertension, diarrhea, interstitial lung disease, and rarely oral mucosal lesions. Here, we presented an unusual case of gingival overgrowth associated with the use of leflunomide, which improved after ceasing the drug.

  18. Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome.

    Science.gov (United States)

    Valenti, Daniela; de Bari, Lidia; Vigli, Daniele; Lacivita, Enza; Leopoldo, Marcello; Laviola, Giovanni; Vacca, Rosa Anna; De Filippis, Bianca

    2017-07-15

    Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that neurobehavioral and brain molecular alterations can be rescued in a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family, crucially involved in the regulation of brain structural plasticity and cognitive processes, can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective agonist. The present study extends previous findings by demonstrating that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial respiratory chain impairment, oxidative phosphorylation deficiency and the reduced energy status in the brain of heterozygous female mice from two highly validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211 treatment completely restored the radical species overproduction by brain mitochondria in the MeCP2-308 model and partially recovered the oxidative imbalance in the more severely affected MeCP2-Bird model. These results provide the first evidence that RTT brain mitochondrial dysfunction can be rescued targeting the brain 5-HT7R and add compelling preclinical evidence of the potential therapeutic value of LP-211 as a pharmacological approach for this devastating neurodevelopmental disorder. Copyright © 2017. Published by Elsevier Ltd.

  19. Risk of dry eye syndrome in patients treated with whole-brain radiotherapy.

    Science.gov (United States)

    Nanda, Tavish; Wu, Cheng-Chia; Campbell, Ashley A; Bathras, Ryan M; Jani, Ashish; Kazim, Michael; Wang, Tony J C

    2017-08-04

    With improvements in systemic therapy, patients with cancer treated with whole-brain radiotherapy (WBRT) are living long enough to develop late toxicities, including dry eye syndrome. In general practice, dose to the lacrimal gland (LG) is not constrained (maximum constraint <40 Gy) in WBRT. The purpose of this study was to measure dose to the LG in WBRT and determine methods for reducing radiation exposure. We conducted a retrospective review of 70 3-dimensional (3D) conformal plans; thirty-six plans with a radiation prescription of 30 Gy in 10 fractions and 34 plans with a prescription of 37.5 Gy in 15 fractions. LGs were contoured in accordance with Freedman and Sidani (2015). Biological effective dose (BED)3 maximum constraints were calculated from 40 Gy and 20 Gy to be 32.17 Gy (30 Gy) and 36.70 Gy (37.5 Gy). Both regimens demonstrated supraorbital blocking by 3 methods: T1, bordering the supraorbital ridge; T2, no contact with supraorbital ridge; and T3, coverage of the supraorbital ridge. Mean dose for the plans with a 30-Gy prescription and the plans with a 37.5-Gy prescription was 27.5 Gy and 35.2 Gy, respectively (p ≤ 0.0001). BED3 maximum constraint (Dmax) was violated 16 of 26 (61.5%) in T1 (average Dmax: 32.2 Gy), 13 of 28 (46.4%) in T2 (average Dmax: 32.1 Gy), and 5 of 18 (27.8%) in T3 (average Dmax: 31.8 Gy) for the 30-Gy prescription. Dmax was violated in 32 of 32 (100%) in T1 (average Dmax: 40.1 Gy), 22 of 22 (100%) in T2 (average Dmax: 40.3 Gy), and 14 of 14 (100%) in T3 (average Dmax: 39.4) for the 37.5 Gy prescription. Average Dmax for the 37.5-Gy prescription was highly significant in favor of T3 (p = 0.0098). Patients who receive WBRT may develop dry eye syndrome as a late toxicity. Constraints are commonly violated with a prescription of 37.5 Gy. Methods to reduce dose include T3 supraorbital blocking, an easily implementable change that may dramatically improve patient quality of life. Copyright © 2017

  20. Does Carbohydrate Challenge Testing Predict Clinical Response in Small Intestinal Bacterial Overgrowth?

    Science.gov (United States)

    Long, Sara K; Di Palma, Jack A

    2016-05-01

    Small intestinal bacterial overgrowth (SIBO) is considered a frequent cause of abdominal symptoms in patients with surgically altered intestinal anatomy or dysmotility conditions and is recognized as a contributing factor in the exacerbation of irritable bowel syndrome symptoms. Diagnostic testing can be used to detect the condition. The study group comprised patients who had breath hydrogen and methane lactulose challenge testing. All of the patients were treated with antibiotic regimens that have shown benefit for SIBO. The lactulose challenge was administered orally at 15 g. Hydrogen and methane in expired air were measured and hydrogen values were recorded as the hydrogen plus twice the methane result. Breath tests were analyzed for positivity based on single and multiple criteria of fasting baseline elevation, early rise, and second peak hydrogen rise. Global improvement of gastrointestinal symptoms was assessed by telephone contact or record review. One hundred participants (78 women) were included in the analysis. The mean age was 51 years. A total of 15% of participants did not meet any criteria on breath testing for SIBO; 73% had a fasting baseline elevation >10 ppm; and 19% had an increase of >20 ppm above baseline in the first 20 minutes, 48% had a 20-ppm increase in the first 60 minutes, and 32% had a second increase, reflecting a colon peak. Overall, 74% responded to a course of antibiotics, determined by reported improvement in more than half of the symptoms within 3 months. In total, 67% (10/15) of the subjects who tested negative for SIBO, by all criteria, had a favorable response to antibiotics. Among those with positive hydrogen increases, 76.3% with 1 criterion responded, 66.7% with 2 criteria responded, 84.6% with 3 responded, and 76.9% with 4 responded. After antibiotic treatment, 88.7% (47/53) of those who had diarrhea reported improvement, 63.3% (19/30) with constipation reported improvement, and 74.3% (52/70) with baseline bloating

  1. Role of bacterial overgrowth in the stomach as an additional risk factor for gastritis.

    Science.gov (United States)

    Naylor, Gregory; Axon, Anthony

    2003-06-01

    Gastric bacteria can either be ingested or ascend from the distal bowel; however, their survival is usually limited by gastric acidity and motility. A reduction in gastric acid can result in bacterial overgrowth in the stomach and proximal small bowel, and the number of organisms rises as the intragastric pH rises. The increased risk of noncardia gastric cancer seen in patients with hypochlorhydria may be explained by an excess of nitrites and N-nitroso compounds (NOCs). These compounds are found in the diet of populations with a high gastric cancer risk, but can also be produced by the organisms that exist in the hypochlorhydria stomach. It has long been hypothesized that nitrites and NOCs act as one of the triggers in the atrophy-metaplasia-dysplasia-carcinoma path. However, although indirect data have linked the premalignant changes of metaplasia and dysplasia to NOCs, direct measurement of gastric nitrites and NOCs has not confirmed such a link. The role of Helicobacter pylori in bacterial overgrowth is mainly as a cause of hypochlorhydria resulting from atrophic gastritis, leading to a reduction in the parietal cell mass. Acid-suppressing drugs can result in bacterial overgrowth and increased nitrites and NOCs, although there is no current evidence for an increased risk of gastric cancer in patients taking them. One explanation is that the stomach appears to be colonized by different organisms than those in patients with hypochlorhydria for other reasons. There is some evidence that bacterial overgrowth per se can cause gastric inflammation in mice; however, although in humans the degree of gastric inflammation is greater when overgrowth is more prominent this may simply reflect the greater degree of hypochlorhydria in patients with a more severe H pylori-induced inflammation.

  2. 'Overgrowth' mutants in barley and wheat: new alleles and phenotypes of the 'Green Revolution' DELLA gene.

    Science.gov (United States)

    Chandler, Peter Michael; Harding, Carol Anne

    2013-04-01

    A suppressor screen using dwarf mutants of barley (Hordeum vulgare L.) led to the isolation of 'overgrowth' derivatives, which retained the original dwarfing gene but grew at a faster rate because of a new mutation. The new mutations were in the Slender1 (Sln1) gene (11/13 cases), which encodes the DELLA protein central to gibberellin (GA) signalling, showed 100% genetic linkage to Sln1 (1/13), or were in the Spindly1 (Spy1) gene (1/13), which encodes another protein involved in GA signalling. The overgrowth mutants were characterized by increased GA signalling, although the extent still depended on the background GA biosynthesis capacity, GA receptor function, and DELLA activity. A comparison between two GA responses, α-amylase production and leaf growth rate, revealed degrees of specificity for both the overgrowth allele and the GA response under consideration. Many overgrowth mutants were also isolated in a dwarf line of bread wheat (Triticum aestivum L.) and 19 new alleles were identified in the Rht-B1 gene, one of the 'Green Revolution' semi-dwarfing genes and the orthologue of Sln1. The sites of amino acid substitutions in the DELLA proteins of both species provide insight into DELLA function, and included examples where identical but independent substitutions were observed. In both species, the starting lines were too dwarfed to be directly useful in breeding programmes, but new overgrowth derivatives with semidwarf heights have now been characterized. The variation they exhibit in GA-influenced traits identifies novel alleles with perfect markers that are of potential use in breeding.

  3. Efficacy of AZM therapy in patients with gingival overgrowth induced by Cyclosporine A: a systematic review

    Directory of Open Access Journals (Sweden)

    Deli Giorgio

    2008-12-01

    Full Text Available Abstract Background In daily clinical practice of a dental department it's common to find gingival overgrowth (GO in periodontal patients under treatment with Cyclosporine A (CsA. The pathogenesis of GO and the mechanism of action of Azithromycin (AZM are unclear. A systematic review was conducted in order to evaluate the efficacy of Azithromycin in patients with gingival overgrowth induced by assumption of Cyclosporine A. Methods A bibliographic search was performed using the online databases MEDLINE, EMBASE and Cochrane Central of Register Controlled Trials (CENTRAL in the time period between 1966 and September 2008. Results The literature search retrieved 24 articles; only 5 were Randomised Controlled Trials (RCTs, published in English, fulfilled the inclusion criteria. A great heterogeneity between proposed treatments and outcomes was found, and this did not allow to conduct a quantitative meta-analysis. The systematic review revealed that a 5-day course of Azithromycin with Scaling and Root Planing reduces the degree of gingival overgrowth, while a 7-day course of metronidazole is only effective on concomitant bacterial over-infection. Conclusion Few RCTs on the efficacy of systemic antibiotic therapy in case of GO were found in the literature review. A systemic antibiotic therapy without plaque and calculus removal is not able to reduce gingival overgrowth. The great heterogeneity of diagnostic data and outcomes is due to the lack of precise diagnostic methods and protocols about GO. Future studies need to improve both diagnostic methods and tools and adequate classification aimed to determine a correct prognosis and an appropriate therapy for gingival overgrowth.

  4. Deep brain stimulation for Tourette syndrome: a single-center series.

    Science.gov (United States)

    Dowd, Richard S; Pourfar, Michael; Mogilner, Alon Y

    2017-04-07

    OBJECTIVE Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS. METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient's pre- and postoperative images. RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up. CONCLUSIONS The authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

  5. Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.

    Science.gov (United States)

    Li, B U; Balint, J P

    2000-01-01

    Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the

  6. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation.

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved; Bar-Gad, Izhar

    2015-07-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. Copyright © 2015 the American Physiological Society.

  7. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice.

    Science.gov (United States)

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J; Curry, Daniel J; Samaco, Rodney C; Zoghbi, Huda Y; Tang, Jianrong

    2015-10-15

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.

  8. Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome.

    Directory of Open Access Journals (Sweden)

    Juliet A Moncaster

    2010-05-01

    Full Text Available Down syndrome (DS, trisomy 21 is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21 encoding the Alzheimer's disease (AD amyloid precursor protein (APP. Triplication of the APP gene accelerates APP expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Abeta, early-onset AD neuropathology, and age-dependent cognitive sequelae. The DS phenotype complex also includes distinctive early-onset cerulean cataracts of unknown etiology. Previously, we reported increased Abeta accumulation, co-localizing amyloid pathology, and disease-linked supranuclear cataracts in the ocular lenses of subjects with AD. Here, we investigate the hypothesis that related AD-linked Abeta pathology underlies the distinctive lens phenotype associated with DS. Ophthalmological examinations of DS subjects were correlated with phenotypic, histochemical, and biochemical analyses of lenses obtained from DS, AD, and normal control subjects. Evaluation of DS lenses revealed a characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear Abeta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic Abeta aggregates (approximately 5 to 50 nm identical to the lens pathology identified in AD. Peptide sequencing, immunoblot analysis, and ELISA confirmed the identity and increased accumulation of Abeta in DS lenses. Incubation of synthetic Abeta with human lens protein promoted protein aggregation, amyloid formation, and light scattering that recapitulated the molecular pathology and clinical features observed in DS lenses. These results establish the genetic etiology of the distinctive lens phenotype in DS and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder. Moreover, these findings confirm increased Abeta

  9. Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Perminder S Sachdev

    Full Text Available BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS of the antero-medial globus pallidus interna (GPi for severe Tourette Syndrome (TS in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6% patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1, transient anxiety (2, dizziness (1, poor balance (1 and worsening of stuttering (1. CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

  10. Effects of a functional COMT polymorphism on brain anatomy and cognitive function in adults with velo-cardio-facial syndrome.

    Science.gov (United States)

    van Amelsvoort, T; Zinkstok, J; Figee, M; Daly, E; Morris, R; Owen, M J; Murphy, K C; De Haan, L; Linszen, D H; Glaser, B; Murphy, D G M

    2008-01-01

    Velo-cardio-facial syndrome (VCFS) is associated with deletions at chromosome 22q11, abnormalities in brain anatomy and function, and schizophrenia-like psychosis. Thus it is assumed that one or more genes within the deleted region are crucial to brain development. However, relatively little is known about how genetic variation at 22q11 affects brain structure and function. One gene on 22q11 is catechol-O-methyltransferase (COMT): an enzyme that degrades dopamine and contains a functional polymorphism (Val158Met) affecting enzyme activity. Here, we investigated the effect of COMT Val158Met polymorphism on brain anatomy and cognition in adults with VCFS. The COMT Val158Met polymorphism was genotyped for 26 adults with VCFS on whom DNA was available. We explored its effects on regional brain volumes using hand tracing approaches; on regional grey- and white-matter density using computerized voxel-based analyses; and measures of attention, IQ, memory, executive and visuospatial function using a comprehensive neuropsychological test battery. After corrections for multiple comparisons Val-hemizygous subjects, compared with Met-hemizygotes, had a significantly larger volume of frontal lobes. Also, Val-hemizygotes had significantly increased grey matter density in cerebellum, brainstem, and parahippocampal gyrus, and decreased white matter density in the cerebellum. No significant effects of COMT genotype on neurocognitive performance were found. COMT genotype effects on brain anatomy in VCFS are not limited to frontal regions but also involve other structures previously implicated in VCFS. This suggests variation in COMT activity is implicated in brain development in VCFS.

  11. Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

    Science.gov (United States)

    Hamann, Stephan; Stevens, Jennifer; Vick, Janice Hassett; Bryk, Kristina; Quigley, Charmian A; Berenbaum, Sheri A; Wallen, Kim

    2014-11-01

    Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Script generation and the dysexecutive syndrome in patients with brain injury

    NARCIS (Netherlands)

    Boelen, Danielle H. E.; Allain, Philippe; Spikman, Jacoba M.; Fasotti, Luciano

    2011-01-01

    Objective: The authors investigated whether patients with brain injury suffering from dysexecutive symptoms had difficulties with script generation. Method: Forty-eight patients with brain injury of various etiology with complaints of executive dysfunctioning and deficient scores on executive tests

  13. Sotos syndrome (cerebral gigantism: analysis of 8 cases

    Directory of Open Access Journals (Sweden)

    Melo Débora Gusmão

    2002-01-01

    Full Text Available Sotos syndrome or cerebral gigantism is characterized by macrocephaly, overgrowth, mental retardation and central nervous system abnormalities. Congenital heart defects may be present. We report 8 patients with this syndrome and relate their clinical features, neuroimaging and echocardiographic findings.

  14. Klippel-Trenaunay-Weber Syndrome:A case report

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Kyung Nam; Lee, Sun Wha; Yoon, Yup; Lim, Jae Hoon [Kyung Hee University Hopital, Seoul (Korea, Republic of)

    1990-10-15

    The Klippel-Trenauna-Weber Syndrome is characterized by a classical triad that includes unilateral cutaneous capillary hemangiomas, varicose veins, and local gigantism with both soft tissue and osseous overgrowth. Authors have experience on case of Klippel-Trenaunay-Weber Syndrome with hemangiomas of ipsilateral scrotum and foot.

  15. Gut Microbiota and the Gut-Brain Axis : New Insights in the Pathophysiology of Metabolic Syndrome

    NARCIS (Netherlands)

    de Clercq, Nicolien C.; Frissen, Myrthe N.; Groen, Albert K.; Nieuwdorp, Max

    2017-01-01

    Objective: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut

  16. Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome

    NARCIS (Netherlands)

    de Clercq, Nicolien C.; Frissen, Myrthe N.; Groen, Albert K.; Nieuwdorp, Max

    2017-01-01

    Objective: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut

  17. Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Weiss, Daniel; Mielke, Carina; Wächter, Tobias; Bender, Benjamin; Liscic, Rajka M; Scholten, Marlieke; Naros, Georgios; Plewnia, Christian; Gharabaghi, Alireza; Krüger, Rejko

    2015-03-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) presents as complex movement disorder including tremor and cerebellar ataxia. The efficacy and safety of deep brain stimulation of the nucleus ventralis intermedius of the thalamus in atypical tremor syndromes like FXTAS remains to be determined. Here, we report the long-term outcome of three male genetically confirmed FXTAS patients treated with bilateral neurostimulation of the nucleus ventralis intermedius for up to four years. All patients demonstrated sustained improvement of both tremor and ataxia - the latter included improvement of intention tremor and axial tremor. Kinematic gait analyses further demonstrated a regularization of the gait cycle. Initial improvements of hand functional disability were not sustained and reached the preoperative level of impairment within one to two years from surgery. Our data on patients with a genetic cause of tremor show favorable outcome and may contribute to improved patient stratification for neurostimulation therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A Late Onset of Adrenocortical Cancer Assosiated with Beckwith-Wiedemann Syndrome

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    N S Kuznetsov

    2014-06-01

    Full Text Available Beckwith-Wiedemann syndrome (BWS is a genetic overgrowth disorder involving a predisposition to tumor development. The common features of Beckwith-Wiedemann syndrome include omphalocele, macroglos- sia and macrosomia. The increased risk for neoplasia is concentrated in the first eight years of life. However, this case presents a late onset of adrenocortical cancer assosiated with Beckwith-Wiedemann syndrome.

  19. Neuro-behavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, A.; Malan, V.; De Blois, M.C.; Colleaux, L.; Munnich, A. [Hop Necker Enfants Malad, Assistance Publ Hop Paris, Natl Inst Hlth and Med Res, Paris (France); Philippe, A.; De Blois, M.C.; Colleaux, L.; Munnich, A. [HopNecker Enfants Malad, Assistance Publ Hop Paris, Dept Genet, Paris (France); Boddaert, N. [Natl Inst Hlth and Med Res, Mixed Unit Res 0205, Orsay (France); Vaivre-Douret, L.; Robel, L.; Golse, B. [Hop Necker Enfants Malad, Assistance Publ Hop Paris, Dept Psychiat, Paris (France); Vaivre-Douret, L. [Univ Paris 10, Mixed Unit Res S0669, Univ Paris 05, Univ Paris 11, Paris 10 (France); Vaivre-Douret, L. [Assistance Publ Hop Paris, Dept Obstet et Gynaecol, Paris (France); Danon-Boileau, L. [Natl Ctr Sci Res, Mixed Unit Res 7114, Paris (France); Heron, D. [Hop La Pitie Salpetriere, Assistance Publ HopParis, Dept Genet, Paris (France)

    2008-07-01

    The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neuro-developmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains under-diagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neuro-behavioral phenotype and brain abnormalities of this micro-deletional syndrome. We assessed neuro-motor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion. Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages similar to 3 to 5 years; sensory processing dysfunction; and neuro-motor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion. The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely under-diagnosed condition. (authors)

  20. Sex differences in protein expression in the mouse brain and their perturbations in a model of Down syndrome

    OpenAIRE

    Block, Aaron; Ahmed, Md. Mahiuddin; Dhanasekaran, A. Ranjitha; Tong, Suhong; Gardiner, Katheleen J.

    2015-01-01

    Background While many sex differences in structure and function of the mammalian brain have been described, the molecular correlates of these differences are not broadly known. Also unknown is how sex differences at the protein level are perturbed by mutations that lead to intellectual disability (ID). Down syndrome (DS) is the most common genetic cause of ID and is due to trisomy of human chromosome 21 (Hsa21) and the resulting increased expression of Hsa21-encoded genes. The Dp(10)1Yey mous...

  1. Sudden onset of Cotard’s syndrome as a clinical sign of brain tumor

    OpenAIRE

    Gonçalves, Luís Francisco Moreira; Tosoni, Alberto

    2016-01-01

    Letter to the editor [Excerpt] We report the clinical case where the sudden onset of a Cotard syndrome in a 69 year old lady lead to the discovery of a multifocal glioblastoma in the right temporo-parietal lobe. Cotard’s syndrome is a rare psychiatric disorder in which the afflicted patient believes he or she is dead. These nihilistic thoughts are the expression of a rare syndrome first described by Jules Cotard in late XIX century. The Cotard’s syndrome has been studied and it seems that ...

  2. Mild Traumatic Brain Injury and Post-concussion Syndrome: Treatment and Related Sequela for Persistent Symptomatic Disease.

    Science.gov (United States)

    Bramley, Harry; Hong, Justin; Zacko, Christopher; Royer, Christopher; Silvis, Matthew

    2016-09-01

    Sport-related concussion typically resolves within a few weeks of the injury; however, persistent symptoms have been reported to occur in 10% to 15% of concussions. These ongoing symptoms can cause significant disability and be frustrating for the patient and family. In addition, factors other than brain injury can cause complications for these patients, such as adjustment disorder or exacerbation of preexisting conditions such as depression or migraine. Individuals with prolonged symptoms of concussion may be classified as having post-concussion syndrome. A careful and thoughtful evaluation is important, as the clinician must determine whether these prolonged symptoms reflect brain injury pathophysiology versus another process. Although there have been numerous studies on the acute management of concussion, much less is available on the treatment of persistent disease. This review will provide an evaluation approach for the patient with prolonged concussion symptoms and review recent literature on treatment strategies.

  3. Treatment of persistent post-concussion syndrome due to mild traumatic brain injury: current status and future directions.

    Science.gov (United States)

    Hadanny, Amir; Efrati, Shai

    2016-08-01

    Persistent post-concussion syndrome caused by mild traumatic brain injury has become a major cause of morbidity and poor quality of life. Unlike the acute care of concussion, there is no consensus for treatment of chronic symptoms. Moreover, most of the pharmacologic and non-pharmacologic treatments have failed to demonstrate significant efficacy on both the clinical symptoms as well as the pathophysiologic cascade responsible for the permanent brain injury. This article reviews the pathophysiology of PCS, the diagnostic tools and criteria, the current available treatments including pharmacotherapy and different cognitive rehabilitation programs, and promising new treatment directions. A most promising new direction is the use of hyperbaric oxygen therapy, which targets the basic pathological processes responsible for post-concussion symptoms; it is discussed here in depth.

  4. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van [Department of Radiology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Ceulemans, Berten; Laridon, Annick [Department of Pediatric Neurology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Jorens, Philippe G. [Department of Pediatric Intensive Care Medicine, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2003-12-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  5. Diffusion Tensor Imaging Findings in Post-Concussion Syndrome Patients After Mild Traumatic Brain Injury: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Edrea Khong

    2016-09-01

    Full Text Available Objectives: To review the evidence for the use of diffusion tensor imaging (DTI parameters in the human brain as a diagnostic tool for and predictor of post-concussion syndrome (PCS after a mild traumatic brain injury (mTBI.Design: Systematic review.Data Sources: All relevant studies in AMED, Embase, MEDLINE, Ovid, PubMed, Scopus, and Web of Science through 20 May 2016.Study Selection: Studies that analyze traditional DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity and the severity of PCS symptoms or the development of PCS in humans after an mTBI.Data Extraction: Population studied, patient source, mTBI diagnosis method, PCS diagnosis method, DTI values measured, significant findings, and correlation between DTI findings and PCS.Data Synthesis: 10 studies investigated correlations between DTI values and PCS symptom severity or between DTI values and the development of PCS in mTBI patients. Decreased fractional anisotropy and increased mean diffusivity and radial diffusivity were associated with the development and severity of PCS. Axial diffusivity was not found to change significantly. Brain regions found to have significant changes in DTI parameters varied from study to study, although the corpus callosum was most frequently cited as having abnormal DTI parameters in PCS patients.Conclusion: DTI abnormalities correlate with PCS incidence and symptom severity, as well as indicate an increased risk of developing PCS after mTBI. Abnormal DTI findings should prompt investigation of the syndrome to ensure optimal symptom management at the earliest stages. Currently, there is no consensus in the literature about the use of one DTI parameter in a specific region of the brain as a biomarker for PCS because no definite trends for DTI parameters in PCS subjects have been identified. Further research is required to establish a standard biomarker for PCS.

  6. Moebius syndrome.

    OpenAIRE

    J Gordon Millichap

    1990-01-01

    Brain stem calcification on CT scan, suggesting prenatal brain stem ischemia, is reported in an infant with Moebius syndrome examined in the Department of Pediatrics and Neonatal Medicine, State University of Gent, Gent, Belgium.

  7. Ohtahara Syndrome

    Science.gov (United States)

    ... a focal brain lesion (damage contained to one area of the brain) surgery may be beneficial. Other therapies are ... Wernicke-Korsakoff Syndrome Information Page NINDS Whiplash Information Page ...

  8. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial.

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    Rahav Boussi-Gross

    Full Text Available Traumatic brain injury (TBI is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments.The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS. The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week, 60 minutes each, with 100% oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements.HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage.ClinicalTrials.gov NCT00715052.

  9. Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age.

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    Pfefferbaum, Adolf; Rosenbloom, Margaret J; Sassoon, Stephanie A; Kemper, Carol A; Deresinski, Stanley; Rohlfing, Torsten; Sullivan, Edith V

    2012-09-01

    Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity. Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects. This design enabled examination of independent and combined effects of HIV infection and alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]-defining events, hepatitis C infection, age) on regional brain volumes derived from T1-weighted magnetic resonance images. Brain volumes, expressed as Z scores corrected for intracranial volume and age, were measured in 20 tissue and 5 ventricular and sulcal regions. The most profound and consistent volume deficits occurred with alcohol use disorders, notable in the cortical mantle, insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes than control subjects. HIV disease-related factors associated with greater volume abnormalities included CD4 cell count nadir, clinical staging, history of AIDS-defining events, infection age, and current age. Longer sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities in both alcohol groups. Having HIV infection with alcoholism and AIDS had an especially poor outcome on brain structures. That longer periods of sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities encourages the inclusion of alcohol recovery efforts in HIV/AIDS therapeutic settings. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

    Science.gov (United States)

    Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

    2016-01-01

    Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

  11. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    Science.gov (United States)

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  12. Cortical Brain Morphology in Young, Estrogen-Naive, and Adolescent, Estrogen-Treated Girls with Turner Syndrome

    Science.gov (United States)

    Lepage, Jean-Francois; Mazaika, Paul K.; Hong, David S.; Raman, Mira; Reiss, Allan L.

    2013-01-01

    Turner syndrome (TS) is a genetic condition that permits direct investigation of the complex interaction among genes, hormones, behavior, and brain development. Here, we used automated segmentation and surface-based morphometry to characterize the differences in brain morphology in children (n = 30) and adolescents (n = 16) with TS relative to age- and sex-matched control groups (n = 21 and 24, respectively). Our results show that individuals with TS, young and adolescent, present widespread reduction of gray matter volume, white matter volume and surface area (SA) over both parietal and occipital cortices bilaterally, as well as enlarged amygdala. In contrast to the young cohort, adolescents with TS showed significantly larger mean cortical thickness and significantly smaller total SA compared with healthy controls. Exploratory developmental analyses suggested aberrant regional brain maturation in the parahippocampal gyrus and orbitofrontal regions from childhood to adolescence in TS. These findings show the existence of abnormal brain morphology early in development in TS, but also suggest the presence of altered neurodevelopmental trajectories in some regions, which could potentially be the consequences of estrogen deficiency, both pre- and postnatally. PMID:22806268

  13. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS

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    Johnston Jennifer

    2011-07-01

    Full Text Available Abstract Background Bardet-Biedl syndrome (BBS is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1 normal intracranial volume; 2 reduced white matter in all regions of the brain, but most in the occipital region; 3 preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4 reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5 increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes

  14. Gastrointestinal complaints in runners are not due to small intestinal bacterial overgrowth

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    Bärtsch Peter

    2011-07-01

    Full Text Available Abstract Background Gastrointestinal complaints are common among long distance runners. We hypothesised that small intestinal bacterial overgrowth (SIBO is present in long distance runners frequently afflicted with gastrointestinal complaints. Findings Seven long distance runners (5 female, mean age 29.1 years with gastrointestinal complaints during and immediately after exercise without known gastrointestinal diseases performed Glucose hydrogen breath tests for detection of SIBO one week after a lactose hydrogen breath test checking for lactose intolerance. The most frequent symptoms were diarrhea (5/7, 71% and flatulence (6/7, 86%. The study was conducted at a laboratory. In none of the subjects a pathological hydrogen production was observed after the intake of glucose. Only in one athlete a pathological hydrogen production was measured after the intake of lactose suggesting lactose intolerance. Conclusions Gastrointestinal disorders in the examined long distance runners were not associated with small intestinal bacterial overgrowth.

  15. EGFR/ARF6 regulation of Hh signalling stimulates oncogenic Ras tumour overgrowth.

    Science.gov (United States)

    Chabu, Chiswili; Li, Da-Ming; Xu, Tian

    2017-03-10

    Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling. Blocking any step of this signalling cascade inhibits Hh signalling and correspondingly suppresses the growth of both, fly and human cancer cells harbouring oncogenic Ras mutations. These findings highlight a non-canonical Egfr signalling mechanism, centered on Arf6 as a novel regulator of Hh signalling. This explains both, the puzzling requirement of Egfr in oncogenic Ras-mediated overgrowth and the cooperation between Egfr and Hedgehog.

  16. Transglutaminase 2 expression is significantly increased in cyclosporine-induced gingival overgrowth

    OpenAIRE

    Asioli, Sofia; Righi, Alberto; Cardone, Pietro; Aimetti, Mario; Maletta, Francesca; Coda, Renato; Carossa, Stefano; Navone, Roberto; Cassoni, Paola

    2011-01-01

    Cyclosporine A is a potent immunosuppressant used to prevent organ transplant rejection and treat various autoimmune diseases. However, cyclosporine A can also induce gingival overgrowth, which is characterized by increased extracellular matrix due to an altered balance between collagen synthesis and degradation. This study proposed to verify whether trans-glutaminase 2, an enzyme thought to be responsible for the assembly and remodelling of extracellular matrix, plays any role in the path...

  17. Is periodontal health a predictor of drug-induced gingival overgrowth? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ruchi Banthia

    2014-01-01

    Full Text Available Background: Gingival overgrowth is a common side-effect of amlodipine regimen on the oral cavity. There is controversy regarding the cause and effect relationship of periodontal health and drug induced gingival overgrowth. Therefore, this study was conducted to investigate and to assess the relationship between the periodontal health and the onset and severity of gingival overgrowth in hypertensive patients receiving amlodipine. Materials and Methods: A total of 99 known hypertensive patients on amlodipine regimen were included in this study. Probing pocket depth (PPD and clinical attachment loss (CAL were noted on four sites of maxillary and mandibular anterior teeth. Gingival enlargement scores were assessed for each patient by employing the hyperplastic index. Oral hygiene status was evaluated using the calculus index (CI. Patients were divided into H, E and L groups based on their periodontal status and responders and non-responders based on their hyperplastic index scores. Differences in means of different periodontal variables in different groups were tested for significance by using ANOVA and unpaired Student t-test. Pearson′s correlation coefficient was calculated to assess the correlation between different variables. For all analyses, P < 0.05 was considered to be significant. Results: All the periodontal parameters were statistically highly significant (P = 0.00 amongst H, E and L groups and between responders and non-responders. Statistically highly significant Pearson correlation coefficients were found between mean PPD and mean hyperplastic score, mean CAL and mean hyperplastic score and mean calculus and mean hyperplastic score. Conclusion: The results of this study indicated a definite association between periodontal health and development and severity of amlodipine-induced gingival overgrowth

  18. Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole.

    Science.gov (United States)

    Paiva, S A; Sepe, T E; Booth, S L; Camilo, M E; O'Brien, M E; Davidson, K W; Sadowski, J A; Russell, R M

    1998-09-01

    Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P 0.05). The mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

  19. Hyperammonemic Induced Coma by Bacterial Overgrowth in a Child With Hirschsprung's Disease.

    Science.gov (United States)

    Farahmand, Fatemeh; Khodadad, Ahmad; Fallahi, Gholamhosein; Motaharizad, Davood; Sabery Nejad, Javad

    2016-09-01

    Cases with Hirschsprung's disease show the functional intestinal obstruction. Obstruction in these patients may lead to bacterial overgrowth with stasis and inflammation of the colon. Bacterial overgrowth can cause hyperammonemia that makes lethargy and loss of conscious and finally admitting in ICU. The purpose of this case report is to present a case that had Hirschsprung's disease and referred to Children's Medical Center with serum hyper-ammonium caused by bacterial overgrowth that induced coma and altered level of consciousness then made her to admit to PICU. A 15-year-old female referred to Children's Medical Center with lethargy and low grade diarrhea. She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU. Laboratory findings showed hyperammonemia in this case, but other criteria were normal. Administration of antibiotic and lactulose therapy was started that lead to a reduction in serum ammonium level and discharging of the case. Thirteen days later she referred again with mentioned symptoms, and clinical evaluations showed high serum ammonium level. This time because of loss of conscious she had to admit at PICU and used NG tube. Administration of lactulose syrup and sodium benzoate make her in a better condition. Narrowing rectum toward the sigmoid and highly enlarged intestinal lopes was on behalf of Hirschsprung's disease. Finally, the patient with the acceptable situation and oral periodic metronidazole discharged. It is essential to check serum ammonium level in the cases with loss of conscious. The choice for controlling hyperammonemia is lactulose therapy.

  20. Immunoexpression of interleukin-6 in drug-induced gingival overgrowth patients

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    P R Ganesh

    2016-01-01

    Full Text Available Background: To analyze the role of proinflammatory cytokines in drug-induced gingival enlargement in Indian population. Aim: To evaluate for the presence of interleukin-6 (IL-6 in drug-induced gingival enlargement and to compare it with healthy control in the absence of enlargement. Materials and Methods: Thirty-five patients selected for the study and divided into control group (10 and study group (25 consisting of phenytoin (10; cyclosporin (10 and nifedipine (5 induced gingival enlargement. Gingival overgrowth index of Seymour was used to assess overgrowth and allot groups. Under LA, incisional biopsy done, tissue sample fixed in 10% formalin and immunohistochemically evaluated for the presence of IL-6 using LAB-SA method, Labeled- Streptavidin-Biotin Method (LAB-SA kit from Zymed- 2nd generation LAB-SA detection system, Zymed Laboratories, CA. The results of immunohistochemistry were statistically analyzed using Kruskaal–Wallis and Mann–Whitney test. Results: The data obtained from immunohistochemistry assessment shows that drug-induced gingival overgrowth (DIGO samples express more IL-6 than control group and cyclosporin expresses more IL-6 followed by phenytoin and nifedipine. Conclusion: Increased IL-6 expression was noticed in all three DIGO groups in comparison with control group. Among the study group, cyclosporin expressed maximum IL-6 expression followed by phenytoin and nifedipine.

  1. A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the "post-inflammatory brain syndrome" PIBS.

    Science.gov (United States)

    Rathbone, Alasdair Timothy Llewelyn; Tharmaradinam, Surejini; Jiang, Shucui; Rathbone, Michel P; Kumbhare, Dinesh A

    2015-05-01

    Post-concussion syndrome is an aggregate of symptoms that commonly present together after head injury. These symptoms, depending on definition, include headaches, dizziness, neuropsychiatric symptoms, and cognitive impairment. However, these symptoms are common, occurring frequently in non-head injured controls, leading some to question the existence of post-concussion syndrome as a unique syndrome. Therefore, some have attempted to explain post-concussion symptoms as post-traumatic stress disorder, as they share many similar symptoms and post-traumatic stress disorder does not require head injury. This explanation falls short as patients with post-concussion syndrome do not necessarily experience many key symptoms of post-traumatic stress disorder. Therefore, other explanations must be sought to explain the prevalence of post-concussion like symptoms in non-head injury patients. Many of the situations in which post-concussion syndrome like symptoms may be experienced such as infection and post-surgery are associated with systemic inflammatory responses, and even neuroinflammation. Post-concussion syndrome itself has a significant neuroinflammatory component. In this review we examine the evidence of neuroinflammation in post-concussion syndrome and the potential role systemic inflammation plays in post-concussion syndrome like symptoms. We conclude that given the overlap between these conditions and the role of inflammation in their etiologies, a new term, post-inflammatory brain syndromes (PIBS), is necessary to describe the common outcomes of many different inflammatory insults. The concept of post-concussion syndrome is in its evolution therefore, the new term post-inflammatory brain syndromes provides a better understanding of etiology of its wide-array of symptoms and the wide array of conditions they can be seen in. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Differences in {sup 99m}Tc-HMPAO brain SPET perfusion imaging between Tourette's syndrome and chronic tic disorder in children

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, N.-T.; Lee, B.-F. [Dept. of Nuclear Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Taiwan); Chang, Y.-C. [Dept. of Pediatrics, Kaohsiung Chang Kang Children' s Hospital, Kaohsiung, Taiwan (Taiwan); Huang, C.-C. [Dept. of Pediatrics, College of Medicine, National Cheng Kung University, Tainan (Taiwan); Wang, S.-T. [Dept. of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan (Taiwan)

    2001-02-01

    Early differential diagnosis between Tourette's syndrome and chronic tic disorder is difficult but important because both the outcome and the treatment of these two childhood-onset diseases are distinct. We assessed the sensitivity and specificity of brain single-photon emission tomography (SPET) perfusion imaging in distinguishing the two diseases, and characterized their different cerebral perfusion patterns. Twenty-seven children with Tourette's syndrome and 11 with chronic tic disorder (mean age 9.5 and 8.6 years, respectively) underwent brain SPET with technetium-99m hexamethylpropylene amine oxime (HMPAO). Visual interpretation and semi-quantitative analysis of SPET images were performed. On visual interpretation, 22 of 27 (82%) of the Tourette's syndrome group had lesions characterized by decreased perfusion. The left hemisphere was more frequently involved. None of the children with chronic tic disorder had a visible abnormality. Semi-quantitative analysis showed that, compared with children with chronic tic disorder, children with Tourette's syndrome had significantly lower perfusion in the left lateral temporal area and asymmetric perfusion in the dorsolateral frontal, lateral and medial temporal areas. In conclusion, using the visual approach, brain SPET perfusion imaging is sensitive and specific in differentiating Tourette's syndrome and chronic tic disorder. The perfusion difference between the two groups, demonstrated by semi-quantitative analysis, may be related more to the co-morbidity in Tourette's syndrome than to tics per se. (orig.)

  3. [Connective tissue growth factors, CTGF and Cyr61 in drug-induced gingival overgrowth--an animal model].

    Science.gov (United States)

    Ciobanică, Mihaela; Cianga, Corina; Căruntu, Irina-Draga; Grigore, Georgiana; Cianga, P

    2008-01-01

    Human gingival overgrowth may occur as a side effect of chronic administration of some therapeutic agents. The mechanisms responsible for the gingival tissues lesions, fibrosis and inflamation, involve an impaired balance between the production and the degradation of type I collagen. It has been demonstrated that CCN2/CTGF, a connective tissue growth factor, is highly expressed in the gingival tissues and positively correlated with the degree of fibrosis in the drug-induced gingival overgrowth. The aim of this study was to identify the presence and localization of CCN2/CTGF and CCN1/Cyr61, members of the same molecular family, in gingival tissues of cyclosporin A- and nifedipine-treated rats, by immunohistochemistry. Staining was evaluated with light microscope and the results show cellular and extracellular CTGF in nifedipin gingival overgrowth tissues with intensity of labeling higher compared to the CsA gingival overgrowth tissues or the controls. The staining for Cyr61 shows its intracellular localization with no diference of labeling intensity between drug-induced gingival overgrowth and normal tissues. Also, we were interested in the gingival TGF-â expression in those animals. We didn't find any commercial anti-rat TGF antibody and our anti-human antibody shows no cross-reactivity with rat tissues. The data from our study sustain the involvement of CTGF and Cyr61 as growth factors in the gingival tissues and the CTGF association with drug-induced gingival overgrowth.

  4. Proteus Syndrome

    Science.gov (United States)

    ... affect any part of the body but commonly affects the bones and skin. Overgrowth of a bone can cause orthopedic problems, and overgrowth of the skin can cause cosmetic and other concerns. Less commonly, individuals with Proteus ...

  5. Manipulating an internal pulse generator until twiddler's syndrome in a patient treated with deep brain stimulation for obsessive-compulsive disorder.

    Science.gov (United States)

    Franzini, Andrea; Ranieri, Rebecca; Gambini, Orsola; Messina, Giuseppe

    2018-02-01

    Twiddler's syndrome consists of rotation or manipulation of an implantable pulse generator (IPG) in its subcutaneous pocket by a patient, thus causing hardware malfunction. This syndrome is being reported more frequently in patients treated with deep brain stimulation (DBS). We report the case of a woman who had received bed nucleus of stria terminalis (BNST) electrodes for obsessive-compulsive disorder (OCD) and developed twiddler's syndrome a few months after surgery, causing hardware malfunction due to obsessive manipulation of the IPG. The patient did not have compulsions related to touching objects at admission, thus making it difficult to foresee and prevent TS.

  6. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    Directory of Open Access Journals (Sweden)

    Mikkel Wallentin

    2016-01-01

    Full Text Available Klinefelter syndrome (47, XXY (KS is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49 responded to whether the words “GREEN” or “RED” were displayed in green or red (incongruent versus congruent colors. One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying “GREEN” or “RED” had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.

  7. Metabolic Syndrome, Insulin Resistance and Cognitive Dysfunction: Does your metabolic profile affect your brain?

    DEFF Research Database (Denmark)

    Neergaard, Jesper S; Møller, Katrine Dragsbæk; Christiansen, Claus

    2017-01-01

    Dementia and type 2 diabetes are both characterized by long prodromal phases challenging the study of potential risk factors and their temporal relation. The progressive relation between metabolic syndrome, insulin resistance, and dementia has recently been questioned, wherefore the aim...

  8. Comprehensive Analyses of Molecules with Altered Expression in the Brain of a Mouse Model of Down Syndrome for Identification of Pharmacotherapeutic Targets.

    Science.gov (United States)

    Ishihara, Keiichi

    2017-01-01

    Down syndrome, caused by the triplication of human chromosome 21, is the most frequent genetic cause of mental retardation. Mice with a segmental trisomy for mouse chromosome 16, which is orthologous to human chromosome 21, exhibit abnormalities similar to those in individuals with Down syndrome and therefore offer the opportunity for a genotype-phenotype correlation. In the current review, I present several mouse lines with trisomic regions of various lengths and discuss their usefulness for elucidating the mechanisms underlying Down syndrome-associated developmental cognitive disabilities. In addition, our recent comprehensive study attempting to identify molecules with disturbed expression in the brain of a mouse model of Down syndrome in order to develop a pharmacologic therapy for Down syndrome is described.

  9. Classification of Parkinsonian syndromes from FDG-PET brain data using decision trees with SSM/PCA features.

    Science.gov (United States)

    Mudali, D; Teune, L K; Renken, R J; Leenders, K L; Roerdink, J B T M

    2015-01-01

    Medical imaging techniques like fluorodeoxyglucose positron emission tomography (FDG-PET) have been used to aid in the differential diagnosis of neurodegenerative brain diseases. In this study, the objective is to classify FDG-PET brain scans of subjects with Parkinsonian syndromes (Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy) compared to healthy controls. The scaled subprofile model/principal component analysis (SSM/PCA) method was applied to FDG-PET brain image data to obtain covariance patterns and corresponding subject scores. The latter were used as features for supervised classification by the C4.5 decision tree method. Leave-one-out cross validation was applied to determine classifier performance. We carried out a comparison with other types of classifiers. The big advantage of decision tree classification is that the results are easy to understand by humans. A visual representation of decision trees strongly supports the interpretation process, which is very important in the context of medical diagnosis. Further improvements are suggested based on enlarging the number of the training data, enhancing the decision tree method by bagging, and adding additional features based on (f)MRI data.

  10. Complex Regional Pain Syndrome is associated with structural abnormalities in pain-related regions of the human brain

    Science.gov (United States)

    Barad, Meredith J; Ueno, Takefumi; Younger, Jarred; Chatterjee, Neil; Mackey, Sean

    2014-01-01

    Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities, and frequently motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging (sMRI) to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls . Analyses were carried out using a whole brain voxel-based morphometry (VBM) approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems. PMID:24212070

  11. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2014-04-01

    The irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder world wide that lasts for decades. The human gut harbors a diverse population of microbial organisms which is symbiotic and important for well being. However, studies on conventional, germ-free, and obese animals have shown that alteration in normal commensal gut microbiota and an increase in pathogenic microbiota-termed "dysbiosis", impact gut function, homeostasis, and health. Diarrhea, constipation, visceral hypersensitivity, and abdominal pain arise in IBS from the gut-induced dysfunctional metabolic, immune, and neuro-immune communication. Dysbiosis in IBS is associated with gut inflammation. Gut-related inflammation is pivotal in promoting endotoxemia, systemic inflammation, and neuroinflammation. A significant proportion of IBS patients chronically consume alcohol, non-steroidal anti-inflammatories, and fatty diet; they may also suffer from co-morbid respiratory, neuromuscular, psychological, sleep, and neurological disorders. The above pathophysiological substrate is underpinned by dysbiosis, and dysfunctional bidirectional "Gut-Brain Axis" pathways. Pathogenic gut microbiota-related systemic inflammation (due to increased lipopolysaccharide and pro-inflammatory cytokines, and barrier dysfunction), may trigger neuroinflammation enhancing dysfunctional brain regions including hippocampus and cerebellum. These as well as dysfunctional vago-vagal gut-brain axis may promote cognitive impairment. Indeed, inflammation is characteristic of a broad spectrum of neurodegenerative diseases that manifest demntia. It is argued that an awareness of pathophysiological impact of IBS and implementation of appropriate therapeutic measures may prevent cognitive impairment and minimize vulnerability to dementia.

  12. Sex Differences of Brain Serotonin Synthesis in Patients with Irritable Bowel Syndrome Using α-[11C]methyl-L-tryptophan, Positron Emission Tomography and Statistical Parametric Mapping

    Directory of Open Access Journals (Sweden)

    Akio Nakai

    2003-01-01

    Full Text Available BACKGROUND: Irritable bowel syndrome (IBS is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT, a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS.

  13. N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

    NARCIS (Netherlands)

    Windhausen, Fons; Hirsch, Alexander; Sanders, Gerard T.; Cornel, Jan Hein; Fischer, Johan; van Straalen, Jan P.; Tijssen, Jan G. P.; Verheugt, Freek W. A.; de Winter, Robbert J.

    2007-01-01

    BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this

  14. N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.

    NARCIS (Netherlands)

    Windhausen, F.; Hirsch, A.; Sanders, G.T.B.; Cornel, J.H.; Fischer, J.; Straalen, J.P. van; Tijssen, J.G.P.; Verheugt, F.W.A.; Winter, R.J. de

    2007-01-01

    BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this

  15. Dietary Omega-3 Fatty Acid Deficiency and High Fructose Intake in the Development of Metabolic Syndrome, Brain Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-07-01

    Full Text Available Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS. Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD, promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health.

  16. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

    2015-01-01

    To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  17. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Christian-Alexandre Castellano

    Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  18. Influence of Uncertain Anticipation on Brain Responses to Aversive Rectal Distension in Patients With Irritable Bowel Syndrome.

    Science.gov (United States)

    Kano, Michiko; Muratsubaki, Tomohiko; Morishita, Joe; Kono, Keiji; Mugikura, Shunji; Takase, Kei; Ly, Huynh Giao; Dupont, Patrick; Van Oudenhove, Lukas; Fukudo, Shin

    We investigated whether certainty and uncertainty of impending aversive visceral sensation differently modulate regional brain activity, both during anticipation and visceral sensation in irritable bowel syndrome (IBS) patients compared with healthy controls. Twenty-six IBS patients (14 women) and 29 healthy controls (15 women) were enrolled in a functional magnetic resonance imaging study. Participants received rectal distention at an individually titrated severe discomfort level that was preceded by visual cues to induce certain (100% chance of distention), uncertain (50% chance), and safe (0% chance) anticipation. Subjective ratings of anticipatory fear before and discomfort during distention were similar between IBS and control participants under cued certainty and uncertainty (p > .05). Uncertain anticipation compared with certain anticipation induced greater activation of anterior midcingulate cortex, thalamus, and visual processing areas in IBS patients compared with controls. Rectal distention after the uncertain, but not certain, cue induced higher activity in the posterior- and midcingulate cortices and the precuneus in IBS compared with controls. Controls exhibited bilateral insula activation during the nondistention period after the uncertain cue compared with the safe cue. IBS patients failed to produce this response, which was possibly due to elevated bilateral insular responses during nondistention after the safe cue. Brain data were significant at a voxel-level threshold of puncorrected value of less than .005 combined with a cluster-level threshold of pFWE-corrected value of less than .05. Preceding uncertainty differentially modulates the brain processing of physiologically identical rectal stimulation in IBS patients. Cue-dependent alterations in brain responses may underlie hypervigilance to visceral sensations in IBS patients.

  19. What Causes Cushing's Syndrome?

    Science.gov (United States)

    ... Share Facebook Twitter Pinterest Email Print What causes Cushing syndrome? Cushing syndrome can develop for two reasons: ... uhs ), thyroid, or thymus How Tumors Can Cause Cushing Syndrome Normally, the pituitary gland in the brain ...

  20. Roald Dahl and the complete locked-in syndrome: "Cold dead body, living brain"

    DEFF Research Database (Denmark)

    Kondziella, Daniel

    2017-01-01

    The classical locked-in syndrome in which partially preserved eye movements allow for communication is well-recognized by most neurologists. Yet, it is much less well-known that patients exist who are clearly conscious but have lost all means of communicating it to the outside world because...... they no longer have any motor output at all. Of note, Roald Dahl, the internationally acclaimed children book author, described this complete locked-in syndrome in one of his short stories, William and Mary (1959), almost half a century before the medical community became aware of this devastating condition...

  1. Evaluating Sensory Processing in Fragile X Syndrome: Psychometric Analysis of the Brain Body Center Sensory Scales (BBCSS).

    Science.gov (United States)

    Kolacz, Jacek; Raspa, Melissa; Heilman, Keri J; Porges, Stephen W

    2018-02-07

    Individuals with fragile X syndrome (FXS), especially those co-diagnosed with autism spectrum disorder (ASD), face many sensory processing challenges. However, sensory processing measures informed by neurophysiology are lacking. This paper describes the development and psychometric properties of a parent/caregiver report, the Brain-Body Center Sensory Scales (BBCSS), based on Polyvagal Theory. Parents/guardians reported on 333 individuals with FXS, 41% with ASD features. Factor structure using a split-sample exploratory-confirmatory design conformed to neurophysiological predictions. Internal consistency, test-retest, and inter-rater reliability were good to excellent. BBCSS subscales converged with the Sensory Profile and Sensory Experiences Questionnaire. However, data also suggest that BBCSS subscales reflect unique features related to sensory processing. Individuals with FXS and ASD features displayed more sensory challenges on most subscales.

  2. Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure – A case report

    Directory of Open Access Journals (Sweden)

    Bagshaw Sean M

    2004-08-01

    Full Text Available Abstract Background Dialysis disequilibrium syndrome (DDS is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD. We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L. Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L (urea-reduction-ratio 71%. Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

  3. Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.

    Science.gov (United States)

    Gripp, Karen W; Zand, Dina J; Demmer, Laurie; Anderson, Carol E; Dobyns, William B; Zackai, Elaine H; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L; Sol-Church, Katia

    2013-10-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay, and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4; 75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. Copyright © 2013 Wiley Periodicals, Inc.

  4. Hyperammonemic Induced Coma by Bacterial Overgrowth in a Child With Hirschsprung’s Disease

    Directory of Open Access Journals (Sweden)

    Fatemeh Farahmand

    2016-10-01

    Full Text Available Cases with Hirschsprung’s disease show the functional intestinal obstruction. Obstruction in these patients may lead to bacterial overgrowth with stasis and inflammation of the colon. Bacterial overgrowth can cause hyperammonemia that makes lethargy and loss of conscious and finally admitting in ICU. The purpose of this case report is to present a case that had Hirschsprung’s disease and referred to Children’s Medical Center with serum hyper-ammonium caused by bacterial overgrowth that induced coma and altered level of consciousness then made her to admit to PICU. A 15-year-old female referred to Children’s Medical Center with lethargy and low grade diarrhea. She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU. Laboratory findings showed hyperammonemia in this case, but other criteria were normal. Administration of antibiotic and lactulose therapy was started that lead to a reduction in serum ammonium level and discharging of the case. Thirteen days later she referred again with mentioned symptoms, and clinical evaluations showed high serum ammonium level. This time because of loss of conscious she had to admit at PICU and used NG tube. Administration of lactulose syrup and sodium benzoate make her in a better condition. Narrowing rectum toward the sigmoid and highly enlarged intestinal lopes was on behalf of Hirschsprung’s disease. Finally, the patient with the acceptable situation and oral periodic metronidazole discharged. It is essential to check serum ammonium level in the cases with loss of conscious. The choice for controlling hyperammonemia is lactulose therapy.

  5. Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis.

    Science.gov (United States)

    Sánchez, E; Casafont, F; Guerra, A; de Benito, I; Pons-Romero, F

    2005-11-01

    Intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. The aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. We included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. The prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The small-intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/- 5.7 cm) than in control animals (p < 0.001). These results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the

  6. Auditory change detection in fragile X syndrome males: A brain potential study

    NARCIS (Netherlands)

    van der Molen, M.J.W.; van der Molen, M.W.; Ridderinkhof, K.R.; Hamel, B.C.J.; Curfs, L.M.G.; Ramakers, G.J.A.

    2012-01-01

    OBJECTIVE: The present study investigated involuntary change detection in a two-tone pre-attentive auditory discrimination paradigm in order to better understand the information processing mechanisms underlying attention deficits in fragile X syndrome (FXS) males. METHODS: Sixteen males with the FXS

  7. Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome

    Science.gov (United States)

    Bjornsson, Hans T.; Benjamin, Joel S.; Zhang, Li; Weissman, Jacqueline; Gerber, Elizabeth E.; Chen, Yi-Chun; Vaurio, Rebecca G.; Potter, Michelle C.; Hansen, Kasper D.; Dietz, Harry C.

    2015-01-01

    Kabuki syndrome is caused by haploinsufficiency for either of two genes that promote the opening of chromatin. If an imbalance between open and closed chromatin is central to the pathogenesis of Kabuki syndrome, agents that promote chromatin opening might have therapeutic potential. We have characterized a mouse model of Kabuki syndrome with a heterozygous deletion in the gene encoding the lysine-specific methyltransferase 2D (Kmt2d), leading to impairment of methyltransferase function. In vitro reporter alleles demonstrated a reduction in histone 4 acetylation and histone 3 lysine 4 trimethylation (H3K4me3) activity in mouse embryonic fibroblasts from Kmt2d+/βGeo mice. These activities were normalized in response to AR-42, a histone deacetylase inhibitor. In vivo, deficiency of H3K4me3 in the dentate gyrus granule cell layer of Kmt2d+/βGeo mice correlated with reduced neurogenesis and hippocampal memory defects. These abnormalities improved upon postnatal treatment with AR-42. Our work suggests that a reversible deficiency in postnatal neurogenesis underlies intellectual disability in Kabuki syndrome. PMID:25273096

  8. Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

    DEFF Research Database (Denmark)

    Wibroe, Morten; Cappelen, Johan; Castor, Charlotte

    2017-01-01

    Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has ...

  9. European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation

    DEFF Research Database (Denmark)

    Müller-Vahl, Kirsten R; Cath, Danielle C; Cavanna, Andrea E

    2011-01-01

    Syndrome (ESSTS). For a narrative review a systematic literature search was conducted and expert opinions of the guidelines group contributed also to the suggestions. Of 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement. However...

  10. Radiologic features of preteus syndrome: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2014-04-15

    Proteus syndrome is a rare congenital hamartomatous condition that is characterized by a wide range of malformations with overgrowth of various tissues. The author reports the case of a Proteus syndrome in a 14-year-old girl who had the unique features of this syndrome including megaspondylodysplasia with resultant scoliosis, leg discrepancy, macrodactyly, clinodactyly, hyperostosis in external auditory meatus, asymmetric megalencephaly, splenomegaly, cystic lung changes, asymmetric soft tissue fat infiltrations and a long, asymmetric face, with descriptions of the radiological features.

  11. Prevalence of small bowel bacterial overgrowth and its association with nutrition intake in nonhospitalized older adults

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Klein, B.; Schecher, K.

    2003-01-01

    OBJECTIVES: To determine the prevalence of small bowel bacterial overgrowth (SBBO) in older adults and to assess whether SBBO is associated with abdominal complaints and nutrient intake. DESIGN: Cross-sectional survey. SETTING: Eight senior residence sites in Stuttgart, Germany. PARTICIPANTS: Older...... adults living independently in senior residence houses. MEASUREMENTS: The prevalence of SBBO was measured in 328 subjects, of whom 294 were aged 61 and older, by measuring hydrogen concentration (parts per million; ppm) in exhaled air after ingestion of 50 g glucose. Anthropometric data were obtained...

  12. Deep Brain Stimulation for Tremor Associated with Underlying Ataxia Syndromes: A Case Series and Discussion of Issues

    Directory of Open Access Journals (Sweden)

    Genko Oyama

    2014-07-01

    Full Text Available Background: Deep brain stimulation (DBS has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy.Methods: A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2, fragile X associated tremor ataxia syndrome (FXTAS, a case of idiopathic ataxia (ataxia not otherwise specified [NOS], spinocerebellar ataxia type 17 (SCA17, and a senataxin mutation (SETX.Results: DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia‐related symptoms.Discussion: DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened.Erratum published on July 27, 2016

  13. Longitudinal clinical and neuro-radiological findings in a patient with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome

    Directory of Open Access Journals (Sweden)

    Yasushi Iwasaki

    2017-09-01

    Full Text Available Since she was 4 years old, the patient had exhibited frequent convulsive seizures, and she experienced severe headaches and depression in adulthood. At the age of 37 years, cerebral calcifications were detected, but she exhibited no cognitive or motor problems. She suffered a cerebral haemorrhage at 49 years old and experienced cognitive dysfunction, dysarthria, dysphagia, and left-hemiparesis as sequelae. After undergoing gastrostomy, she exhibited very slow cognitive deterioration associated with speech disturbance over more than 10 years. She also gradually developed limb spasticity with Babinski signs. Repeated computerised tomography scans revealed unexpected changes including 2 cysts that appeared separately after small haemorrhages, an intracerebral haemorrhage, and intra-cyst bleeding. These longitudinal scans also showed progressive ventricular dilatation and expansion of the leukoencephalopathy, but there were no apparent changes in the intracranial calcifications. Magnetic resonance imaging revealed numerous microbleeds, and magnetic resonance angiography revealed irregularity of the cerebral artery walls with stoppage. Her SNORD118 gene exhibited compound heteromutation of c.38C > G and c.116G > C on different alleles. She was finally diagnosed with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome at the age of 61 years. Past reports have suggested that diffuse cerebral microangiopathy underlies Labrune syndrome's pathogenesis, but we speculate that cerebral macroangiopathy may also underlie it.

  14. Possible compensatory events in adult Down syndrome brain prior to the development of Alzheimer disease neuropathology: targets for nonpharmacological intervention.

    Science.gov (United States)

    Head, E; Lott, I T; Patterson, D; Doran, E; Haier, R J

    2007-03-01

    Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology progressively with age but clinical signs of dementia are delayed by at least 10 years after the first signs of disease. Some individuals with DS do not develop dementia despite extensive AD neuropathology. Given the discordance between clinical decline and AD neuropathology, compensatory events may be of particular relevance for this group. Imaging studies using PET suggest compensatory increases in metabolic rate in vulnerable brain regions in DS prior to the development of dementia. Neurobiological studies of similarly aged DS autopsy cases provide further evidence of activation of plasticity mechanisms. Genes that are overexpressed in DS (APP, DSCAM, MNB/DYRK1A, and RCAN1) produce proteins critical for neuron and synapse growth, development and maintenance. We present the hypothesis that these genes may lead to developmental cognitive deficits but paradoxically with aging, may participate in molecular cascades supporting neuronal compensation. Enhancing or supporting compensatory mechanisms in aging individuals with DS may be beneficial as suggested by intervention studies in animal models. In combination, adults with DS may be a unique group of individuals well-suited for studies involving the manipulation or upregulation of compensatory responses as an approach to promote successful brain aging in the general population.

  15. Baseline brain activity changes in patients with clinically isolated syndrome revealed by resting-state functional MRI

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou; Duan, Yunyun; Liang, Peipeng; Jia, Xiuqin; Yu, Chunshui [Dept. of Radiology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Ye, Jing [Dept. of Neurology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Butzkueven, Helmut [Dept. of Medicine, Univ. of Melbourne, Melbourne (Australia); Dong, Huiqing [Dept. of Neurology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Li, Kuncheng [Dept. of Radiology, Xuanwu Hospital, Capital Medical Univ., Beijing (China); Beijing Key Laboratory of MRI and Brain Informatics, Beijing (China)], E-mail: likuncheng1955@yahoo.com.cn

    2012-11-15

    Background A clinically isolated syndrome (CIS) is the first manifestation of multiple sclerosis (MS). Previous task-related functional MRI studies demonstrate functional reorganization in patients with CIS. Purpose To assess baseline brain activity changes in patients with CIS by using the technique of regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI. Material and Methods Resting-state fMRIs data acquired from 37 patients with CIS and 37 age- and sex-matched normal controls were compared to investigate ALFF differences. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, and T2 lesion volume (T2LV) were further explored. Results Patients with CIS had significantly decreased ALFF in the right anterior cingulate cortex, right caudate, right lingual gyrus, and right cuneus (P < 0.05 corrected for multiple comparisons using Monte Carlo simulation) compared to normal controls, while no significantly increased ALFF were observed in CIS. No significant correlation was found between the EDSS, disease duration, T2LV, and ALFF in regions with significant group differences. Conclusion In patients with CIS, resting-state fMRI demonstrates decreased activity in several brain regions. These results are in contrast to patients with established MS, in whom ALFF demonstrates several regions of increased activity. It is possible that this shift from decreased activity in CIS to increased activity in MS could reflect the dynamics of cortical reorganization.

  16. Altered Brain Functional Connectome in Migraine with and without Restless Legs Syndrome: A Resting-State Functional MRI Study

    Directory of Open Access Journals (Sweden)

    Fu-Chi Yang

    2018-01-01

    Full Text Available BackgroundMigraine is frequently comorbid with restless legs syndrome (RLS, both displaying functional connectivity (FC alterations in multiple brain networks, although the neurological basis of this association is unknown.MethodsWe performed resting-state functional magnetic resonance imaging and network-wise analysis of FC in migraine patients with and without RLS and healthy controls (CRL. Network-based statistics (NBS and composite FC matrix analyses were performed to identify the patterns of FC changes. Correlation analyses were performed to identify associations between alterations in FC and clinical profiles.ResultsNBS results revealed that both migraine patients with and without RLS exhibited lower FC than CRL in the dorsal attention, salience, default mode, cingulo-opercular, visual, frontoparietal, auditory, and sensory/somatomotor networks. Further composite FC matrix analyses revealed differences in FC of the salience, default mode to subcortical and frontoparietal, auditory to salience, and memory retrieval networks between migraine patients with and without RLS. There was a trend toward a negative association between RLS severity and cross-network abnormalities in the default mode to subcortical network.DiscussionMigraine patients with and without RLS exhibit disruptions of brain FC. Such findings suggest that these disorders are associated with differential neuropathological mechanisms and may aid in the future development of neuroimaging-driven biomarkers for these conditions.

  17. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does It Work?

    Science.gov (United States)

    Deeb, Wissam; Rossi, Peter J; Porta, Mauro; Visser-Vandewalle, Veerle; Servello, Domenico; Silburn, Peter; Coyne, Terry; Leckman, James F; Foltynie, Thomas; Hariz, Marwan; Joyce, Eileen M; Zrinzo, Ludvic; Kefalopoulou, Zinovia; Welter, Marie-Laure; Karachi, Carine; Mallet, Luc; Houeto, Jean-Luc; Shahed-Jimenez, Joohi; Meng, Fan-Gang; Klassen, Bryan T; Mogilner, Alon Y; Pourfar, Michael H; Kuhn, Jens; Ackermans, L; Kaido, Takanobu; Temel, Yasin; Gross, Robert E; Walker, Harrison C; Lozano, Andres M; Khandhar, Suketu M; Walter, Benjamin L; Walter, Ellen; Mari, Zoltan; Changizi, Barbara K; Moro, Elena; Baldermann, Juan C; Huys, Daniel; Zauber, S Elizabeth; Schrock, Lauren E; Zhang, Jian-Guo; Hu, Wei; Foote, Kelly D; Rizer, Kyle; Mink, Jonathan W; Woods, Douglas W; Gunduz, Aysegul; Okun, Michael S

    2016-01-01

    Tourette Syndrome (TS) is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS), already widely utilized for Parkinson's disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with DBS worldwide, have delayed regulatory agency approval (e.g., FDA and equivalent agencies around the world). The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

  18. Tumor risk in Beckwith-Wiedemann syndrome : A review and meta-analysis

    NARCIS (Netherlands)

    Rump, P; Zeegers, MPA; van Essen, AJ

    2005-01-01

    Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macroglossia, abdominal wall defects, ear anomalies, and an increased risk for embryonic tumors. Reported tumor risk estimates vary between 4% and 21%. It has been hypothesized that tumor predisposition in BWS is related to

  19. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics

    DEFF Research Database (Denmark)

    Jensen, Anne Skakkebæk; Bojesen, A; Kristensen, M. K.

    2014-01-01

    volume where KS patients with skewed X-chromosome inactivation tended to have smaller brains. Skewed X-inactivation, CAG repeat length and parent-of-origin were not correlated with educational and marital status, personality traits, autism traits, and psychological distress, prevalence of depression...

  20. Microstructural brain injury in post-concussion syndrome after minor head injury

    NARCIS (Netherlands)

    M. Smits (Marion); G.C. Houston (Gavin); D.W.J. Dippel (Diederik); P.A. Wielopolski (Piotr); M.W. Vernooij (Meike); P.J. Koudstaal (Peter Jan); M.G.M. Hunink (Myriam); A. van der Lugt (Aad)

    2011-01-01

    textabstractIntroduction: After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional

  1. Cardiotocographic and Doppler Ultrasonographic Findings in a Fetus with Brain Death Syndrome

    Directory of Open Access Journals (Sweden)

    Yi-Ting Chen

    2006-09-01

    Conclusion: The possibility of intrauterine brain death should be considered in all cases of prolonged fixed FHR pattern, accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness of this event may prevent unnecessary emergency cesarean section.

  2. Volumetric Brain Morphometry Changes in patients with Obstructive Sleep Apnea Syndrome : effects of CPAP treatment and literature review.

    Directory of Open Access Journals (Sweden)

    Nelly T Huynh

    2014-04-01

    Full Text Available Introduction: Obstructive sleep apnea syndrome (OSAS is a frequent breathing disorder occurring during sleep that is characterized by recurrent hypoxic episodes and sleep fragmentation. It remains unclear whether OSAS leads to structural brain changes, and if so, in which brain regions. Brain region-specific gray and white matter volume (GMV and WMV changes can be measured with voxel-based morphometry (VBM. The aims of this study were to use VBM to analyze GMV and WMV in untreated OSAS patients compared to healthy controls (HC; examine the impact of OSAS-related variables (nocturnal hypoxemia duration and sleep fragmentation index on GMV and WMV; and assess the effects of therapeutic versus sham continuous positive airway pressure (CPAP. We discuss our results in light of previous findings and provide a comprehensive literature review. Methods: Twenty-seven treatment-naïve male patients with moderate to severe OSAS and seven healthy age- and education-matched control subjects (HC were recruited. After a baseline fMRI scan, patients randomly received either active (therapeutic, n=14 or sham (subtherapeutic, n=13 nasal CPAP treatment for 2 months. Results: Significant negative correlations were observed between nocturnal hypoxemia duration and GMV in bilateral lateral temporal regions. No differences in GMV or WMV were found between OSAS patients and HC, and no differences between CPAP versus sham CPAP treatment effects in OSAS patients. Conclusion: It appears that considering VBM GMV changes there is little difference between OSAS patients and HC. The largest VBM study to date indicates structural changes in the lateral aspect of the temporal lobe, which also showed a significant negative correlation with nocturnal hypoxemia duration in our study. This finding suggests an association between the effect of nocturnal hypoxemia and decreased GMV in OSAS patients.

  3. Volumetric Brain Morphometry Changes in Patients with Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment and Literature Review.

    Science.gov (United States)

    Huynh, Nelly T; Prilipko, Olga; Kushida, Clete A; Guilleminault, Christian

    2014-01-01

    Obstructive sleep apnea syndrome (OSAS) is a frequent breathing disorder occurring during sleep that is characterized by recurrent hypoxic episodes and sleep fragmentation. It remains unclear whether OSAS leads to structural brain changes, and if so, in which brain regions. Brain region-specific gray and white matter volume (GMV and WMV) changes can be measured with voxel-based morphometry (VBM). The aims of this study were to use VBM to analyze GMV and WMV in untreated OSAS patients compared to healthy controls (HC); examine the impact of OSAS-related variables (nocturnal hypoxemia duration and sleep fragmentation index) on GMV and WMV; and assess the effects of therapeutic vs. sham continuous positive airway pressure (CPAP) treatment. We discuss our results in light of previous findings and provide a comprehensive literature review. Twenty-seven treatment-naïve male patients with moderate to severe OSAS and seven healthy age- and education-matched HC were recruited. After a baseline fMRI scan, patients randomly received either active (therapeutic, n = 14) or sham (subtherapeutic, n = 13) nasal CPAP treatment for 2 months. Significant negative correlations were observed between nocturnal hypoxemia duration and GMV in bilateral lateral temporal regions. No differences in GMV or WMV were found between OSAS patients and HC, and no differences between CPAP vs. sham CPAP treatment effects in OSAS patients. It appears that considering VBM GMV changes there is little difference between OSAS patients and HC. The largest VBM study to date indicates structural changes in the lateral aspect of the temporal lobe, which also showed a significant negative correlation with nocturnal hypoxemia duration in our study. This finding suggests an association between the effect of nocturnal hypoxemia and decreased GMV in OSAS patients.

  4. Brain magnetic resonance imaging pattern and outcome in children with haemolytic-uraemic syndrome and neurological impairment treated with eculizumab.

    Science.gov (United States)

    Gitiaux, Cyril; Krug, Pauline; Grevent, David; Kossorotoff, Manoelle; Poncet, Sarah; Eisermann, Monika; Oualha, Mehdi; Boddaert, Nathalie; Salomon, Remi; Desguerre, Isabelle

    2013-08-01

    The aim of this study was to describe the magnetic resonance imaging (MRI) findings and the neurological and neuropsychological outcomes in paediatric, diarrhoea-associated haemolytic-uraemic syndrome (D+HUS) with central nervous system impairment treated with eculizumab, a monoclonal antibody. The 14-month single-centre prospective study included seven children (three males, four females; age range 16 mo-7 y 8 mo; median age 3 y 7 mo) with typical D+HUS and acute neurological impairment. In the acute phase of the disease, neurological assessment and brain magnetic resonance imaging (MRI), including measurement of the apparent diffusion coefficient (ADC), were performed, and neuropsychological evaluation and brain MRI were also carried out 6 months after disease onset. In the acute phase, basal ganglia and white matter abnormalities with ADC restriction were a common and reversible MRI finding. In all the surviving patients (5/7), follow-up MRI after 6 months was normal, indicating reversible lesions. Clinical and neuropsychological evaluations after 6 months were also normal. This specific brain MRI pattern consisting of an ADC decrease in basal ganglia and white matter without major T2/fluid-attenuated inversion recovery (FLAIR) injury may be a key finding in the acute phase of the disease in favour of a vasculitis hypothesis. These reversible lesions were associated with a good neurological outcome. These results call for further evaluation of the potential role of eculizumab in the choice of treatment for severe D+HUS, particularly in the case of early neurological signs. © 2013 Mac Keith Press.

  5. Roald Dahl and the complete locked-in syndrome: "Cold dead body, living brain".

    Science.gov (United States)

    Kondziella, Daniel

    2017-08-15

    The classical locked-in syndrome in which partially preserved eye movements allow for communication is well-recognized by most neurologists. Yet, it is much less well-known that patients exist who are clearly conscious but have lost all means of communicating it to the outside world because they no longer have any motor output at all. Of note, Roald Dahl, the internationally acclaimed children book author, described this complete locked-in syndrome in one of his short stories, William and Mary (1959), almost half a century before the medical community became aware of this devastating condition. The present clinical commentary highlights an under-recognized and clinically highly relevant topic, exemplified by a lesser-known but stunning piece of literature from one of the most beloved contemporary novelist. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.

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    Hsueh-Tzu Shih

    2016-09-01

    Full Text Available To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.

  7. Stress engineering of high-quality single crystal diamond by heteroepitaxial lateral overgrowth

    Science.gov (United States)

    Tang, Y.-H.; Golding, B.

    2016-02-01

    A method for lateral overgrowth of low-stress single crystal diamond by chemical vapor deposition (CVD) is described. The process is initiated by deposition of a thin (550 nm) (001) diamond layer on Ir-buffered a-plane sapphire. The diamond is partially masked by periodic thermally evaporated Au stripes using photolithography. Lateral overgrowth of the Au occurs with extremely effective filtering of threading dislocations. Thermal stress resulting from mismatch of the low thermal expansion diamond and the sapphire substrate is largely accommodated by the ductile Au layer. The stress state of the diamond is investigated by Raman spectroscopy for two thicknesses: at 10 μm where the film has just overgrown the Au mask and at 180 μm where the film thickness greatly exceeds the scale of the masking. For the 10-μm film, the Raman linewidth shows spatial oscillations with the period of the Au stripes with a factor of 2 to 3 reduction relative to the unmasked region. In a 180-μm thick diamond film, the overall surface stress was extremely low, 0.00 ± 0.16 GPa, obtained from the Raman shift averaged over the 7.5 mm diameter of the crystal at its surface. We conclude that the metal mask protects the overgrown diamond layer from substrate-induced thermal stress and cracking. It is also responsible for low internal stress by reducing dislocation density by several orders of magnitude.

  8. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function.

    Science.gov (United States)

    Leupin, Olivier; Piters, Elke; Halleux, Christine; Hu, Shouih; Kramer, Ina; Morvan, Frederic; Bouwmeester, Tewis; Schirle, Markus; Bueno-Lozano, Manuel; Fuentes, Feliciano J Ramos; Itin, Peter H; Boudin, Eveline; de Freitas, Fenna; Jennes, Karen; Brannetti, Barbara; Charara, Nadine; Ebersbach, Hilmar; Geisse, Sabine; Lu, Chris X; Bauer, Andreas; Van Hul, Wim; Kneissel, Michaela

    2011-06-03

    Humans lacking sclerostin display progressive bone overgrowth due to increased bone formation. Although it is well established that sclerostin is an osteocyte-secreted bone formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a sclerostin interaction partner. Biochemical assays with recombinant proteins confirmed that sclerostin LRP4 interaction is direct. Interestingly, in vitro overexpression and RNAi-mediated knockdown experiments revealed that LRP4 specifically facilitates the previously described inhibitory action of sclerostin on Wnt1/β-catenin signaling. We found the extracellular β-propeller structured domain of LRP4 to be required for this sclerostin facilitator activity. Immunohistochemistry demonstrated that LRP4 protein is present in human and rodent osteoblasts and osteocytes, both presumed target cells of sclerostin action. Silencing of LRP4 by lentivirus-mediated shRNA delivery blocked sclerostin inhibitory action on in vitro bone mineralization. Notably, we identified two mutations in LRP4 (R1170W and W1186S) in patients suffering from bone overgrowth. We found that these mutations impair LRP4 interaction with sclerostin and its concomitant sclerostin facilitator effect. Together these data indicate that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone.

  9. Bone Overgrowth-associated Mutations in the LRP4 Gene Impair Sclerostin Facilitator Function*

    Science.gov (United States)

    Leupin, Olivier; Piters, Elke; Halleux, Christine; Hu, Shouih; Kramer, Ina; Morvan, Frederic; Bouwmeester, Tewis; Schirle, Markus; Bueno-Lozano, Manuel; Ramos Fuentes, Feliciano J.; Itin, Peter H.; Boudin, Eveline; de Freitas, Fenna; Jennes, Karen; Brannetti, Barbara; Charara, Nadine; Ebersbach, Hilmar; Geisse, Sabine; Lu, Chris X.; Bauer, Andreas; Van Hul, Wim; Kneissel, Michaela

    2011-01-01

    Humans lacking sclerostin display progressive bone overgrowth due to increased bone formation. Although it is well established that sclerostin is an osteocyte-secreted bone formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a sclerostin interaction partner. Biochemical assays with recombinant proteins confirmed that sclerostin LRP4 interaction is direct. Interestingly, in vitro overexpression and RNAi-mediated knockdown experiments revealed that LRP4 specifically facilitates the previously described inhibitory action of sclerostin on Wnt1/β-catenin signaling. We found the extracellular β-propeller structured domain of LRP4 to be required for this sclerostin facilitator activity. Immunohistochemistry demonstrated that LRP4 protein is present in human and rodent osteoblasts and osteocytes, both presumed target cells of sclerostin action. Silencing of LRP4 by lentivirus-mediated shRNA delivery blocked sclerostin inhibitory action on in vitro bone mineralization. Notably, we identified two mutations in LRP4 (R1170W and W1186S) in patients suffering from bone overgrowth. We found that these mutations impair LRP4 interaction with sclerostin and its concomitant sclerostin facilitator effect. Together these data indicate that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone. PMID:21471202

  10. Laser-Assisted Periodontal Management of Drug-Induced Gingival Overgrowth under General Anesthesia: A Viable Option

    Directory of Open Access Journals (Sweden)

    Tupili Muralikrishna

    2013-01-01

    Full Text Available Gingival overgrowth/hyperplasia can be attributed to several causes, but drug-induced gingival overgrowth/hyperplasia arises secondarily to prolonged use of antihypertensive drugs, anticonvulsants and immunosuppressants. The management is complex in nature considering the multitude of factors involved such as substitution of drug strict plaque control along with excision of the tissue to be performed under local anesthesia as outpatient. In the recent times, the patient’s psychological fear of the treatment with the use of surgical blade and multiple visits has developed the concept of single visit treatment under general anesthesia incorporating a laser as viable option. The present case highlights the new method of management of gingival overgrowth.

  11. Review article: Small intestinal bacterial overgrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea.

    Science.gov (United States)

    Fan, X; Sellin, J H

    2009-05-15

    Chronic watery diarrhoea is one of the most common symptoms prompting GI evaluation. Recently, new diagnostic considerations have emerged as possible factors in chronic diarrhoea. To review available data regarding diagnosis and treatment of chronic diarrhoea with an emphasis on bacterial overgrowth and bile acid malabsorption. A systematic search of the English language literature of chronic diarrhoea was performed focused on three possible aetiologies of diarrhoea: small intestinal bacterial overgrowth (SIBO), idiopathic bile salt malabsorption (IBAM), gluten responsive enteropathy. Recent studies suggest that SIBO and bile acid malabsorption may have been underestimated as possible causes of chronic watery diarrhoea. Gluten intolerance with negative coeliac serology is a contentious possible cause of watery diarrhoea, but requires further research before acceptance as an entity. In patients with otherwise unexplained chronic watery diarrhoea, small intestinal bacterial overgrowth and bile salt malabsorption should be considered and investigated.

  12. Pulmonary Manifestations and Management of Proteus Syndrome

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    Chia-Ying Li

    2010-05-01

    Full Text Available Proteus syndrome is a very rare, sporadic and congenital condition that is characterized by postnatal mosaic overgrowth. This disorder is thought to be caused by a somatic gene mutation, but the exact etiology is unknown. Commonly involved tissues include connective tissue, bone, skin and the central nervous system. Another less common symptom involves pulmonary emphysematous changes. This report documents a 25-year-old man with Proteus syndrome who presented with progressive exertional dyspnea and asymmetric overgrowth of his extremities. He underwent left pneumonectomy and his postoperative course was uneventful. Lung tissue showed emphysematous changes with multiple bulla formation and scattered calcification. We also review recent literature related to pulmonary manifestations and management of Proteus syndrome.

  13. The overgrowth of Listeria monocytogenes by other Listeria spp. in food samples undergoing enrichment cultivation has a nutritional basis.

    Science.gov (United States)

    Besse, Nathalie Gnanou; Barre, Lena; Buhariwalla, Colin; Vignaud, Marie Léone; Khamissi, Elissa; Decourseulles, Emilie; Nirsimloo, Marjorie; Chelly, Minyar; Kalmokoff, Martin

    2010-01-01

    The isolation of Listeria monocytogenes from food is carried out using a double enrichment. In cases where multiple Listeria species are present within the original sample, L. monocytogenes can be overgrown during enrichment by other species of listeria present in the original sample. From a practical perspective, this can result in a false negative or complicate the ability of public health investigators to match food and clinical isolates. We have further investigated this phenomenon by analysing the growth kinetics of single species and pairs of different species over the ISO 11290-1 enrichment process. The overgrowth of a strain of L. monocytogenes by a strain of Listeria innocua resulted primarily from interactions which occurred in late exponential phase, where it was observed that growth of both strains stopped when the dominant strain reached stationary phase. In a second mixed culture, the dominant L. monocytogenes strain suppressed the exponential growth rate of the second Listeria welshimeri strain. Both findings suggest that the overgrowth could partially be explained in terms of a nutritional competition. Multi-factor analysis of Fraser broth constituents and growth temperatures using both stressed and non-stressed inoculants failed to identify any single factor in the ISO 11290-1 methodology which would contribute to the overgrowth phenomenon in our model system. Furthermore, species was not a significant factor in observed differences in growth parameters among a wider array of strains which had been stressed or not stressed prior to grown in Fraser broths, even though some strains had significantly faster growth rates than others. Limiting diffusion in Fraser broth through the addition of agar significantly reduced the extent of the overgrowth in experiments using mixtures of strains originally isolated from foods where overgrowth had been previously observed. Taken together, these findings support that the overgrowth phenomenon in most instances

  14. Vascular Functions and Brain Integrity in Midlife: Effects of Obesity and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreana P. Haley

    2014-01-01

    Full Text Available Intact cognitive function is the best predictor of quality of life and functional ability in older age. Thus, preventing cognitive decline is central to any effort to guarantee successful aging for our growing population of elderly. The purpose of the work discussed in this outlook paper is to bridge knowledge from basic and clinical neuroscience with the aim of improving how we understand, predict, and treat age- and disease-related cognitive impairment. Over the past six years, our research team has focused on intermediate neuroimaging phenotypes of brain vulnerability in midlife and isolating the underlying physiological mechanisms. The ultimate goal of this work was to pave the road for the development of early interventions to enhance cognitive function and preserve brain integrity throughout the lifespan.

  15. MR of brain involvement in progressive facial hemiatrophy (Romberg disease): Reconsideration of a syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Terstegge, K.; Hosten, N. (Universitaetsklinikum Rudolf Virchow, Berlin (Germany)); Kunath, B. (Klinik und Poliklinik fuer Neurologie, Dresden (Germany)); Felber, S.; Henkes, H. (Universitaetskliniken der Universitaet Homburg (Germany)); Speciali, J.G. (Universidade de Sao Paolo (Brazil))

    1994-01-01

    To gain further insight into the pathogenesis of progressive facial hemiatrophy, a sporadic disease of unclear etiology characterized by shrinking and deformation of one side of the face. We investigated possible brain involvement. MR of the head and face was performed in three female patients with progressive facial hemiatrophy. The central-nervous-system findings were correlated to a clinical protocol and a review of the literature. One patient with epilepsy had abnormal brain findings confined to the cerebral hemisphere homolateral to the facial hemiatrophy. These consisted of monoventricular enlargement, meningocortical dysmorphia, and white-matter changes. These MR findings, and corresponding neuroradiologic data disclosed by the review, indicate that homolateral hemiatrophy occasionally occurs in a subgroup of patients with progressive facial hemiatrophy. The MR features do not seem consistent with an underlying simple or nutritive atrophic process. We propose chronic localized meningoencephalitis with vascular involvement as a possible underlying cause of the occasional brain involvement in progressive facial hemiatrophy. 29 refs., 2 figs.

  16. Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

    DEFF Research Database (Denmark)

    Wibroe, Morten; Cappelen, Johan; Castor, Charlotte

    2017-01-01

    Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has...... standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally...

  17. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

    DEFF Research Database (Denmark)

    Perry, Rachel J; Peng, Liang; Barry, Natasha A

    2016-01-01

    Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota...... in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut...

  18. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.

    Science.gov (United States)

    Perry, Rachel J; Peng, Liang; Barry, Natasha A; Cline, Gary W; Zhang, Dongyan; Cardone, Rebecca L; Petersen, Kitt Falk; Kibbey, Richard G; Goodman, Andrew L; Shulman, Gerald I

    2016-06-09

    Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity.

  19. Whether to Proceed With Deep Brain Stimulator Battery Change in a Patient With Signs of Potential Sepsis and Parkinson Hyperpyrexia Syndrome: A Case Report.

    Science.gov (United States)

    Liu, Chyong-Jy Joyce; Crnkovic, Anica; Dalfino, John; Singh, Leina Yoko

    2017-04-15

    Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic emergency associated with anti- Parkinson medication withdrawal; however, its clinical presentation mimics sepsis. We describe the case of a 69-year-old man with advanced Parkinson disease who presented for exchange of the depleted battery in his subthalamic deep brain stimulator. The patient's preoperative symptoms of fever, rigidity, altered consciousness, and autonomic instability presented a dilemma whether to proceed with battery exchange to treat PHS or postpone surgery due to potential sepsis. The administration of dopaminergic medications, dantrolene, and antipyretic drugs are temporary supportive measures, while prompt restoration of deep brain stimulator function is the most important therapeutic treatment for PHS.

  20. Processos cognitivos e plasticidade cerebral na Síndrome de Down Cognitive processes and brain plasticity in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Minetto Caldeira Silva

    2006-04-01

    discuss some of the recent discoveries related to cognitive processes in Down Syndrome, so as to show how important brain plasticity can be in development and acquisition of knowledge. To this end, we aim to discuss cognitive processes present in Down Syndrome, relating them to general concepts of brain plasticity and look at ways such knowledge can favor learning. We acknowledge that it isn't possible to exhaust the subject, but we do intend to start thinking about this issue. To do so, we begin with a review of the literature, looking at research, from the oldest to the most recent publications, in an attempt to better understand how to make use of these findings.

  1. N-terminal prohormone brain natriuretic peptide (NT-proBNP as a noninvasive marker for restrictive syndromes

    Directory of Open Access Journals (Sweden)

    C. Mady

    2008-08-01

    Full Text Available Constrictive pericarditis (CP and restrictive cardiomyopathy share many similarities in both their clinical and hemodynamic characteristics and N-terminal prohormone brain natriuretic peptide (NT-proBNP is a sensitive marker of cardiac diastolic dysfunction. The objectives of the present study were to determine whether serum NT-proBNP was high in patients with endomyocardial fibrosis (EMF and CP, and to investigate how this relates to diastolic dysfunction. Thirty-three patients were divided into two groups: CP (16 patients and EMF (17 patients. The control group consisted of 30 healthy individuals. Patients were evaluated by bidimensional echocardiography, with restriction syndrome evaluated by pulsed Doppler of the mitral flow and serum NT-proBNP measured by immunoassay and detected by electrochemiluminescence. Spearman correlation coefficient was used to analyze the association between log NT-proBNP and echocardiographic parameters. Log NT-proBNP was significantly higher (P < 0.05 in CP patients (log mean: 2.67 pg/mL; 95%CI: 2.43-2.92 log pg/mL and in EMF patients (log mean: 2.91 pg/mL; 95%CI: 2.70-3.12 log pg/mL compared with the control group (log mean: 1.45; 95%CI: 1.32-1.60 log pg/mL. There were no statistical differences between EMF and CP patients (P = 0.689 in terms of NT-proBNP. The NT-proBNP log tended to correlate with peak velocity of the E wave (r = 0.439; P = 0.060, but not with A wave (r = -0.399; P = 0.112. Serum NT-proBNP concentration can be used as a marker to detect the presence of diastolic dysfunction in patients with restrictive syndrome; however, serum NT-proBNP levels cannot be used to differentiate restrictive cardiomyopathy from CP.

  2. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.

    Science.gov (United States)

    Lenroot, R K; Blumenthal, J D; Wallace, G L; Clasen, L S; Lee, N R; Giedd, J N

    2014-11-01

    Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  3. Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes.

    Science.gov (United States)

    Lu, Hong-Yan; Zhang, Qiang; Wang, Qiu-Xia; Lu, Jun-Ying

    2016-08-01

    To determine the association of histologic chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) with brain injuries in infants born to mothers with preterm premature rupture of membranes. A total of 103 singleton infants born to mothers with preterm premature rupture of membranes were enrolled. The placental inflammation was confirmed by HCA, and FIRS was defined in fetuses with preterm labor and an elevation of the fetal plasma interleukin-6 concentration. Examination of brain images was conducted to confirm the existence of brain injuries. Based on placental HCA and umbilical cord blood interleukin-6 level, all patients were divided into three groups: HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+). Among all infants with preterm premature rupture of membranes, 53.40% were exposed to HCA, 20.38% experienced FIRS, and the overall incidence of brain injuries was 38.83%. The incidence of brain injury in HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+) groups were 20.83%, 41.18%, and 76.19%, respectively. HCA at the advanced grades and stages was associated with increased risk of brain injury. Umbilical cord blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and granulocyte-colony stimulating factor (G-CSF) in premature infants with brain injuries were significantly higher than in those without brain injuries. Infants diagnosed with both HCA and FIRS showed significantly higher levels of IL-8, TNF-α, and G-CSF than those with HCA alone. Preterm infants exposed to severe chorioamnionitis had an increased risk of brain injury. IL-6, IL-8, TNF-α, and G-CSF in cord blood were associated with brain injuries in preterm infants and may be used as extradiagnostic criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

    Science.gov (United States)

    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and

  5. Location of brain lesions predicts conversion of clinically isolated syndromes to multiple sclerosis

    DEFF Research Database (Denmark)

    Giorgio, Antonio; Battaglini, Marco; Rocca, Maria Assunta

    2013-01-01

    and clinical follow-up at 1 year were collected for 1,165 patients with CIS. On T2-weighted MRI, we generated lesion probability maps of white matter (WM) lesion location and frequency. Voxelwise analyses were performed with a nonparametric permutation-based approach (p ...: In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed...

  6. A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study

    Science.gov (United States)

    Misner, Bill D

    2007-01-01

    Background Athlete's Foot (Tinea pedis) is a form of ringworm associated with highly contagious yeast-fungi colonies, although they look like bacteria. Foot bacteria overgrowth produces a harmless pungent odor, however, uncontrolled proliferation of yeast-fungi produces small vesicles, fissures, scaling, and maceration with eroded areas between the toes and the plantar surface of the foot, resulting in intense itching, blisters, and cracking. Painful microbial foot infection may prevent athletic participation. Keeping the feet clean and dry with the toenails trimmed reduces the incidence of skin disease of the feet. Wearing sandals in locker and shower rooms prevents intimate contact with the infecting organisms and alleviates most foot-sensitive infections. Enclosing feet in socks and shoes generates a moisture-rich environment that stimulates overgrowth of pungent both aerobic bacteria and infectious yeast-fungi. Suppression of microbial growth may be accomplished by exposing the feet to air to enhance evaporation to reduce moistures' growth-stimulating effect and is often neglected. There is an association between yeast-fungi overgrowths and disabling foot infections. Potent agents virtually exterminate some microbial growth, but the inevitable presence of infection under the nails predicts future infection. Topical antibiotics present a potent approach with the ideal agent being one that removes moisture producing antibacterial-antifungal activity. Severe infection may require costly prescription drugs, salves, and repeated treatment. Methods A 63-y female volunteered to enclose feet in shoes and socks for 48 hours. Aerobic bacteria and yeast-fungi counts were determined by swab sample incubation technique (1) after 48-hours feet enclosure, (2) after washing feet, and (3) after 8-hours socks-shoes exposure to a aromatic oil powder-compound consisting of arrowroot, baking soda, basil oil, tea tree oil, sage oil, and clove oil. Conclusion Application of this

  7. A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study

    Directory of Open Access Journals (Sweden)

    Misner Bill D

    2007-07-01

    Full Text Available Abstract Background Athlete's Foot (Tinea pedis is a form of ringworm associated with highly contagious yeast-fungi colonies, although they look like bacteria. Foot bacteria overgrowth produces a harmless pungent odor, however, uncontrolled proliferation of yeast-fungi produces small vesicles, fissures, scaling, and maceration with eroded areas between the toes and the plantar surface of the foot, resulting in intense itching, blisters, and cracking. Painful microbial foot infection may prevent athletic participation. Keeping the feet clean and dry with the toenails trimmed reduces the incidence of skin disease of the feet. Wearing sandals in locker and shower rooms prevents intimate contact with the infecting organisms and alleviates most foot-sensitive infections. Enclosing feet in socks and shoes generates a moisture-rich environment that stimulates overgrowth of pungent both aerobic bacteria and infectious yeast-fungi. Suppression of microbial growth may be accomplished by exposing the feet to air to enhance evaporation to reduce moistures' growth-stimulating effect and is often neglected. There is an association between yeast-fungi overgrowths and disabling foot infections. Potent agents virtually exterminate some microbial growth, but the inevitable presence of infection under the nails predicts future infection. Topical antibiotics present a potent approach with the ideal agent being one that removes moisture producing antibacterial-antifungal activity. Severe infection may require costly prescription drugs, salves, and repeated treatment. Methods A 63-y female volunteered to enclose feet in shoes and socks for 48 hours. Aerobic bacteria and yeast-fungi counts were determined by swab sample incubation technique (1 after 48-hours feet enclosure, (2 after washing feet, and (3 after 8-hours socks-shoes exposure to a aromatic oil powder-compound consisting of arrowroot, baking soda, basil oil, tea tree oil, sage oil, and clove oil. Conclusion

  8. Functional orthosis in shoulder joint subluxation after ischaemic brain stroke to avoid post-hemiplegic shoulder-hand syndrome: a randomized clinical trial.

    Science.gov (United States)

    Hartwig, Maik; Gelbrich, Götz; Griewing, Bernd

    2012-09-01

    To examine whether the use of a shoulder joint functional orthosis over four weeks can mitigate the development or progression of the shoulder-hand syndrome in patients with shoulder joint subluxation after stroke. Two-armed randomized controlled trial. Rehabilitation unit of a neurological hospital, single centre. Forty-one patients with caudal subluxation of the glenohumeral joint and hemiparesis of the upper extremity after ischaemic brain stroke. Support by functional orthosis Neuro-Lux (Sporlastic, Nürtingen, Germany) on top of usual care according to current guidelines (experimental, n = 20) versus usual care alone (control, n = 21). Weekly shoulder-hand syndrome scores (severity of clinical symptoms ranging from 0 to 14), discomfort caused by the orthosis, and its usage rate. The primary outcome was the average shoulder-hand syndrome score on days 14, 21 and 28, adjusted for the baseline shoulder-hand syndrome score. The adjusted mean shoulder-hand syndrome score was lower by 3.1 in the intervention compared to the control subjects (95% confidence interval 1.9 to 4.3, P shoulder-hand syndrome. Timing and duration of application of the orthosis as well as its combination with other therapeutic measures should be investigated in future clinical trials.

  9. Hemi-spatial neglect rehabilitation using non-invasive brain stimulation: or how to modulate the disconnection syndrome?

    Science.gov (United States)

    Jacquin-Courtois, S

    2015-09-01

    Hemi-spatial neglect syndrome is common and sometimes long-lasting. It is characterized by a deficit in the use and awareness of one side of space, most often consecutive to a right hemisphere injury, mainly in the parietal region. Acknowledging the different types and all clinical characteristics is essential for an appropriate evaluation and adapted rehabilitation care management, especially as it constitutes a predictive factor of a poor functional prognosis. Some new approaches have been developed in the last fifteen years in the field of hemi-spatial neglect rehabilitation, where non-invasive brain stimulation (TMS and tDCS) holds an important place. Today's approaches of unilateral spatial neglect modulation via non-invasive brain stimulation are essentially based on the concept of inter-hemispheric inhibition, suggesting an over-activation of the contralesional hemisphere due to a decrease of the inhibiting influences of the injured hemisphere. Several approaches may then be used: stimulation of the injured right hemisphere, inhibition of the hyperactive left hemisphere, or a combination of both. Results are promising, but the following complementary aspects must be refined before a more systematic application: optimal stimulation protocol, individual management according to the injured region, intensity, duration and frequency of care management, delay post-stroke before the beginning of treatment, combination of different approaches, as well as prognostic and efficacy criteria. An encouraging perspective for the future is the combination of several types of approaches, which would be largely facilitated by the improvement of fundamental knowledge on neglect mechanisms, which could in the future refine the choice for the most appropriate treatment(s) for a given patient. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Cockayne Syndrome B Protects Against Methamphetamine-Enhanced Oxidative DNA Damage in Murine Fetal Brain and Postnatal Neurodevelopmental Deficits

    Science.gov (United States)

    McCallum, Gordon P.; Wong, Andrea W.

    2011-01-01

    Abstract Methamphetamine (METH) increases the oxidative DNA lesion 8-oxoguanine (8-oxoG) in fetal mouse brain, and causes postnatal motor coordination deficits after in utero exposure. Like oxoguanine glycosylase 1 (OGG1), the Cockayne syndrome B (CSB) protein is involved in the repair of oxidatively damaged DNA, although its function is unclear. Here we used CSB-deficient Csbm/m knockout mice to investigate the developmental role of DNA oxidation and CSB in METH-initiated neurodevelopmental deficits. METH (40 mg/kg intraperitoneally) administration to pregnant Csb females on gestational day 17 increased 8-oxoG levels in Csbm/m fetal brains (p < 0.05). CSB modulated 8-oxoG levels independent of OGG1 activity, as 8-oxoG incision activity in fetal nuclear extracts was identical in Csbm/m and Csb+/+mice. This CSB effect was evident despite 7.1-fold higher OGG1 activity in Csb+/+ mice compared to outbred CD-1 mice. Female Csbm/m offspring exposed in utero to METH exhibited motor coordination deficits postnatally (p < 0.05). In utero METH exposure did not cause dopaminergic nerve terminal degeneration, in contrast to adult exposures. This is the first evidence that CSB protects the fetus from xenobiotic-enhanced DNA oxidation and postnatal functional deficits, suggesting that oxidatively damaged DNA is developmentally pathogenic, and that fetal CSB activity may modulate the risk of reactive oxygen species-mediated adverse developmental outcomes. Antioxid. Redox Signal. 14, 747–756. PMID:20673160

  11. Post-concussion syndrome (PCS) in a youth population: defining the diagnostic value and cost-utility of brain imaging.

    Science.gov (United States)

    Morgan, Clinton D; Zuckerman, Scott L; King, Lauren E; Beaird, Susan E; Sills, Allen K; Solomon, Gary S

    2015-12-01

    Approximately 90% of concussions are transient, with symptoms resolving within 10-14 days. However, a minority of patients remain symptomatic several months post-injury, a condition known as post-concussion syndrome (PCS). The treatment of these patients can be challenging. The goal of our study was to assess the utility and cost-effectiveness of neurologic imaging two or more weeks post-injury in a cohort of youth with PCS. We conducted a retrospective study of 52 pediatric patients with persistent post-concussion symptoms after 3 months. We collected demographics and neuroimaging results obtained greater than 2 weeks post-concussion. Neuroimaging ordered in the first 2 weeks post-concussion was excluded, except to determine the rate of re-imaging. Descriptive statistics and corresponding cost data were collected. Of 52 patients with PCS, 23/52 (44%) had neuroimaging at least 2 weeks after the initial injury, for a total of 32 diagnostic studies. In summary, 1/19 MRIs (5.3%), 1/8 CTs (13%), and 0/5 x-rays (0%) yielded significant positive findings, none of which altered clinical management. Chronic phase neuroimaging estimated costs from these 52 pediatric patients totaled $129,025. We estimate the cost to identify a single positive finding was $21,000 for head CT and $104,500 for brain MRI. In this cohort of pediatric PCS patients, brain imaging in the chronic phase (defined as more than 2 weeks after concussion) was pursued in almost half the study sample, had low diagnostic yield, and had poor cost-effectiveness. Based on these results, outpatient management of pediatric patients with long-term post-concussive symptoms should rarely include repeat neuroimaging beyond the acute phase.

  12. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does it Work?

    Directory of Open Access Journals (Sweden)

    Wissam eDeeb

    2016-04-01

    Full Text Available Tourette Syndrome (TS is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS, already widely utilized for Parkinson’s disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with implanted DBS worldwide, have delayed regulatory agency approval (e.g. FDA and equivalent agencies around the world. The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

  13. Partial trisomy due to a de novo duplication 22q11.1-22q13.1: a cat-eye syndrome variant with brain anomalies.

    Science.gov (United States)

    Karcaaltincaba, D; Ceylaner, S; Ceylaner, G; Dalkilic, S; Karli-Oguz, K; Kandemir, O

    2010-01-01

    We report a case of partial trisomy 22q with de novo duplication of chromosomal region 22q11.1-22q13.1, also confirmed by microarray comparative genomic hybridization (Array-CGH) analysis. The fetus had interhemispheric cyst and corpus callosum agenesis diagnosed by MRI which has not been reported in the literature. This novel phenotype differs from the reported cat eye syndromes by the absence of heart defects and the presence of brain anomalies.

  14. Deep Brain Stimulation of the Globus Pallidus Internus in Patients with Intractable Tourette Syndrome: A 1-year Follow-up Study

    OpenAIRE

    Xiao-Hua Zhang; Jian-Yu Li; Yu-Qing Zhang; Yong-Jie Li

    2016-01-01

    Background: Deep brain stimulation (DBS) has been a promising treatment for patients with refractory Tourette syndrome (TS) for more than a decade. Despite successful DBS treatment of TS in more than 100 patients worldwide, studies with a large patient sample and long-term follow-up assessments are still scarce. Accordingly, we investigated the clinical efficacy and safety of globus pallidus internus (GPi) DBS in the treatment of intractable TS in 24 patients with a 1-year follow-up assessmen...

  15. Cognitive-motor dysfunction after severe traumatic brain injury: A cerebral interhemispheric disconnection syndrome.

    Science.gov (United States)

    Falchook, Adam D; Porges, Eric C; Nadeau, Stephen E; Leon, Susan A; Williamson, John B; Heilman, Kenneth M

    2015-01-01

    In most right-handed people, the left hemisphere is dominant for programming the temporal and spatial "how" (praxis) aspects of purposeful skilled movements, and the right hemisphere is dominant for control of the intentional "when" aspects of actions that mediate initiation, persistence, termination, and inhibition. Since the interhemispheric axons of the corpus callosum are especially susceptible to shearing from torsional forces during traumatic brain injury (TBI), the goal of this study was to learn whether participants with a history of severe traumatic brain injury demonstrate three types of cognitive-motor impairments that may result from callosal injury: ideomotor apraxia of the left hand, limb kinetic apraxia of the left hand, and hypokinesia of the right hand in response to left hemispatial stimuli. Nine participants with severe TBI and nine healthy control participants were studied for the presence of ideomotor apraxia, limb kinetic apraxia, and hypokinesia. When compared to the control participants, the participants with TBI revealed ideomotor apraxia and limb kinetic apraxia of the left hand and hypokinesia in response to left-sided visual stimuli when tested with the right hand. TBI appears to cause unilateral disorders of cognitive-motor functions. Future research is needed to understand how these cognitive-motor disorders are related to interhemispheric disconnection most likely induced by injury to the corpus callosum.

  16. Dysexecutive behaviour following deep brain lesions--a different type of disconnection syndrome?

    Science.gov (United States)

    Krause, Martin; Mahant, Neil; Kotschet, Katya; Fung, Victor S; Vagg, Daniel; Wong, Chong H; Morris, John G L

    2012-01-01

    The suppression of automatic prepotent behaviour in favour of more successful, more 'appropriate' behaviour is the primary function of the frontal lobe. Five frontal-subcortical circuits connect the frontal lobe to the basal ganglia and the thalamus. We report 17 patients with small lesions in the downstream structures of the frontal-subcortical circuits displaying severe dysexecutive behaviour. Positron emission tomography (PET) demonstrated hypometabolism of the frontal lobe in some of these patients. The literature on frontal lobe dysfunction after lesions in the basal ganglia and thalamus is discussed and the semiology of frontal lobe dysfunction in relation to the frontal-subcortical circuits is highlighted. Derived from our findings we suggest a disconnection syndrome of the frontal lobe caused by lesions in the downstream structures of the frontal-subcortical circuits. Crown Copyright © 2011. Published by Elsevier Srl. All rights reserved.

  17. The pattern of amyloid accumulation in the brains of adults with Down syndrome

    Science.gov (United States)

    Annus, Tiina; Wilson, Liam R.; Hong, Young T.; Acosta–Cabronero, Julio; Fryer, Tim D.; Cardenas–Blanco, Arturo; Smith, Robert; Boros, Istvan; Coles, Jonathan P.; Aigbirhio, Franklin I.; Menon, David K.; Zaman, Shahid H.; Nestor, Peter J.; Holland, Anthony J.

    2016-01-01

    Introduction Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. Methods Forty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. Results Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. Discussion PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial. PMID:26362596

  18. The Role of Intestinal Bacteria Overgrowth in Obesity-Related Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Silvia M. Ferolla

    2014-12-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.

  19. AMLODIPIN-INDUCED GINGIVAL OVERGROWTH AND APPLICATION OF ER:YAG LASER IN THE TREATMENT PROTOCOL.

    Directory of Open Access Journals (Sweden)

    Elena I. Firkova

    2013-05-01

    Full Text Available Gingival overgrowth (GO is one of the most important clinical features of gingival pathology. Amlodipine is a comparatively new III generation calcium channels blocker, used for management of cardiovascular disorders. Although it is considered safe, it can also rarely induce GO. A case of severe amlodipine-induced GO, complicated by inflammatory changes due to plaque accumulation is presented in a 54 years old patient.Treatment was performed as follows: drug substitution; initial periodontal therapy –scaling and root planning (reduction of inflammatory component in the gingival tissues; Er:YAG laser-performed gingivectomy and gingivoplasty; maintenance care. The healing process went uneventful and the postoperative results were extremely esthetically and functionally satisfactory.

  20. Oral subcutaneous midline leiomyomatous hamartoma presenting as congenital incisive papilla overgrowth in a toddler

    Directory of Open Access Journals (Sweden)

    Ashish Loomba

    2017-01-01

    Full Text Available Congenital soft-tissue tumors of oral cavity are mostly hyperplastic and benign in nature. This article presents an unusual case of congenital subcutaneous hamartoma of incisive papilla in a 2-year-old female child causing feeding and breathing difficulty. Total excisional biopsy was done under local anesthesia. Histopathology of tissue in reticulin-stained slide showed the presence of immature muscle fibers whereas Masson's trichrome stain revealed collagen fibers and smooth muscles confirming the diagnosis of oral midline subcutaneous smooth muscle (leiomyomatous hamartoma of incisive papilla. It is important for dental professionals to be aware of this oral lesion present from birth mimicking overgrowth of incisive papilla, by its presentation, differential diagnosis, histopathology, and management.

  1. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth.

    Science.gov (United States)

    Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

    2015-08-01

    To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5. HF/HS diet increased maternal fat mass by 2.2-fold (P Maternal circulating insulin, leptin, and cholesterol were increased (P maternal obesity. © 2015 The Obesity Society.

  2. Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus

    DEFF Research Database (Denmark)

    Llorente, Cristina; Jepsen, Peter; Inamine, Tatsuo

    2017-01-01

    fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease......Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic...... in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans...

  3. Dislocation propagation in GaN films formed by epitaxial lateral overgrowth

    Science.gov (United States)

    Sakai; Sunakawa; Kimura; Usui

    2000-01-01

    We have investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) the relationship between surface morphological evolution and dislocation propagation in GaN films formed by epitaxial lateral overgrowth (ELO) in hydride vapour phase epitaxy. The SEM observations revealed that step and terrace structures were formed on (0001) surfaces of the films both in the earlier and the later stages of growth, suggesting the occurrence of step-flow growth during ELO. Bending dislocations with laterally propagated segments were frequently observed in the ELO films and their morphology led to a reduction in threading dislocation density in the film surface regions. Systematic TEM observations were performed to reveal the detailed structure of the bending dislocations. Comparison between the SEM and the TEM results showed that the lateral propagation of the dislocation was closely related to the appearance of the [1101) facets. A mechanism for dislocation propagation is discussed that explains the observed dislocation structure and surface step morphology.

  4. Stromal Overgrowth in a Brenner Tumor or Ovarian Fibroma With Minor Sex Cord Elements?

    Science.gov (United States)

    Ross, Julia A; Saglam, Ozlen

    2015-07-01

    Computed tomography obtained as part of a urinary tract assessment in a 68-year-old woman incidentally detected a solid adnexal mass. Bilateral salpingo-oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor.

  5. Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome.

    Science.gov (United States)

    Vasiadi, Magdalini; Newman, Jennifer; Theoharides, Theoharis C

    2014-10-31

    Chronic Fatigue Syndrome (CFS) is a neuroimmunoendocrine disease affecting about 1% of the US population, mostly women. It is characterized by debilitating fatigue for six or more months in the absence of cancer or other systemic diseases. Many CFS patients also have fibromyalgia and skin hypersensitivity that worsen with stress. Corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted under stress, activate mast cells (MC) necessary for allergic reactions to release inflammatory mediators that could contribute to CFS symptoms. To investigate the effect of isoflavones on the action of polyinosinic:polycytidylic acid (poly(I:C)), with or without swim stress, on mouse locomotor activity and inflammatory mediator expression, as well as on human MC activation. Female C57BL/6 mice were randomly divided into four groups: (a) control/no-swim, (b) control/swim, (c) polyinosinic:polycytidylic acid (poly(I:C))/no swim, and (d) polyinosinic:polycytidylic acid (poly(I:C))/swim. Mice were provided with chow low or high in isoflavones for 2 weeks prior to ip injection with 20 mg/kg poly(I:C) followed or not by swim stress for 15 minutes. Locomotor activity was monitored overnight and animals were sacrificed the following day. Brain and skin gene expression, as well as serum levels, of inflammatory mediators were measured. Data were analyzed using the non-parametric Mann-Whitney U-test. Poly(I:C)-treated mice had decreased locomotor activity over 24 hours, and increased serum levels of TNF-α, IL-6, KC (IL-8/CXCL8 murine homolog), CCL2,3,4,5, CXCL10, as well as brain and skin gene expression of TNF, IL-6, KC (Cxcl1, IL8 murine homolog), CCL2, CCL4, CCL5 and CXCL10. Histidine decarboxylase (HDC) and NT expression were also increased, but only in the skin, over the same period. High isoflavone diet reversed these effects. Poly(I:C) treatment decreased mouse locomotor activity and increased serum levels and brain and skin gene expression of inflammatory mediators

  6. Deep brain stimulation in Gilles de la Tourette syndrome: killing several birds with one stone? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Andreas Hartmann

    2016-09-01

    Full Text Available In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS, deep brain stimulation (DBS of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction.

  7. DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome.

    Science.gov (United States)

    Marsh, Ashley P L; Edwards, Timothy J; Galea, Charles; Cooper, Helen M; Engle, Elizabeth C; Jamuar, Saumya S; Méneret, Aurélie; Moutard, Marie-Laure; Nava, Caroline; Rastetter, Agnès; Robinson, Gail; Rouleau, Guy; Roze, Emmanuel; Spencer-Smith, Megan; Trouillard, Oriane; Billette de Villemeur, Thierry; Walsh, Christopher A; Yu, Timothy W; Heron, Delphine; Sherr, Elliott H; Richards, Linda J; Depienne, Christel; Leventer, Richard J; Lockhart, Paul J

    2018-01-01

    The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome (DSBS). Although the underlying molecular mechanisms leading to disease remain poorly understood, they are thought to stem from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC mutations associated with abnormal CNS development in humans, including 14 missense and 12 predicted loss-of-function mutations, and discuss their associated clinical characteristics and diagnostic features. We provide an update on the observed genotype-phenotype relationships of congenital mirror movements, isolated ACC and DSBS, and correlate this to our current understanding of the biological function of DCC in the development of the CNS. All mutations and their associated phenotypes were deposited into a locus-specific LOVD (https://databases.lovd.nl/shared/genes/DCC). © 2017 Wiley Periodicals, Inc.

  8. Serum level of brain-derived neurotrophic factor in fibromyalgia syndrome correlates with depression but not anxiety.

    Science.gov (United States)

    Nugraha, Boya; Korallus, Christoph; Gutenbrunner, Christoph

    2013-02-01

    Brain-derived neurotrophic factor (BDNF) has been known to play a role in fibromyalgia syndrome (FMS) patients. Depression and anxiety are quite common additional symptoms in FMS. However the role of BDNF in these symptoms still needs to be elucidated. Although BDNF has been shown to be relevant in major depression, however studies could not show such differences between FMS patients with and without major depression. As mood-related symptom occurs frequently and differs in its intensity in FMS patients, BDNF level should be measured in subgroup regarding depression and anxiety scale. Therefore the aim of this study was to evaluate the correlation of BDNF in serum of FMS with intensity of depression and anxiety. Additionally, interleukin (IL)-6 was measured. This study showed that serum level of BDNF was age-dependent in HCs. FMS patients had higher level of serum BDNF as compared to HC. Additionally, serum level of BDNF showed correlation with depression, but not with anxiety. Serum level of BDNF increased with depression score in FMS. However, serum level of IL-6 was not correlated with both depression and anxiety scores. Taken together, BDNF is involved in the pathophysiology of FMS. Additionally, it seems to be correlated with intensity of depressive symptoms in FMS. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

    Science.gov (United States)

    Maling, Nicholas; Hashemiyoon, Rowshanak; Foote, Kelly D; Okun, Michael S; Sanchez, Justin C

    2012-01-01

    Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.

  10. Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions.

    Science.gov (United States)

    Hyland, Niall P; Quigley, Eamonn M M; Brint, Elizabeth

    2014-07-21

    Irritable bowel syndrome (IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.

  11. Structural brain alterations of Down's syndrome in early childhood evaluation by DTI and volumetric analyses

    Energy Technology Data Exchange (ETDEWEB)

    Gunbey, Hediye Pinar; Bilgici, Meltem Ceyhan; Aslan, Kerim; Incesu, Lutfi [Ondokuz Mayis University, Faculty of Medicine, Department of Radiology, Kurupelit, Samsun (Turkey); Has, Arzu Ceylan [Bilkent University, National Magnetic Resonance Research Center, Ankara (Turkey); Ogur, Methiye Gonul [Ondokuz Mayis University, Department of Genetics, Samsun (Turkey); Alhan, Aslihan [Ufuk University, Department of Statistics, Ankara (Turkey)

    2017-07-15

    To provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down's syndrome (DS). Ten children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes. Children with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05). These preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development. (orig.)

  12. Diagnostic value of brain chronic black holes on T1-weighted MR images in clinically isolated syndromes.

    Science.gov (United States)

    Mitjana, Raquel; Tintoré, Mar; Rocca, Maria A; Auger, Cristina; Barkhof, Frederik; Filippi, Massimo; Polman, Chris; Fazekas, Franz; Huerga, Elena; Montalban, Xavier; Rovira, Alex

    2014-10-01

    Non-enhancing black holes (neBHs) are more common in multiple sclerosis (MS) patients with longer disease durations and progressive disease subtypes. Our aim was to analyse the added value of neBHs in patients with clinically isolated syndromes (CISs) for predicting conversion to clinically definite MS (CDMS). Patients were classified based on the presence or absence of neBHs and on the number of Barkhof-Tintoré (B-T) criteria fulfilled. Dissemination in space (DIS) was defined as the presence of at least three of the four B-T criteria. Dissemination in time (DIT)1 was defined by simultaneous presence of enhancing and non-enhancing lesions. DIT2 was defined by simultaneous presence of neBHs and T2 lesions not apparent on T1-weighted images. Focal T2-hyperintense brain lesions were identified in 87.7% of the 520 CIS patients, and 41.4% of them presented at least one neBH. Patients meeting DIS, DIT1, and DIT2 had a significantly higher rate of conversion to CDMS. After adjusting for DIS, only patients who fulfilled DIT1 preserved a significant increase in CDMS conversion. Non-enhancing black holes in CIS patients are associated with a higher risk of conversion to CDMS. However, the predictive value of this finding is lost when added to the DIS criteria. © The Author(s) 2014.

  13. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

    Directory of Open Access Journals (Sweden)

    Nicholas Maling

    Full Text Available Tourette syndrome (TS is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.

  14. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

    Science.gov (United States)

    Krauer, Fabienne; Riesen, Maurane; Reveiz, Ludovic; Oladapo, Olufemi T; Martínez-Vega, Ruth; Porgo, Teegwendé V; Haefliger, Anina; Broutet, Nathalie J; Low, Nicola

    2017-01-01

    The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain-Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose-response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose-response relationship and specificity), we found that more than half the relevant studies supported a causal

  15. Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain–Barré Syndrome: Systematic Review

    Science.gov (United States)

    Reveiz, Ludovic; Oladapo, Olufemi T.; Martínez-Vega, Ruth; Haefliger, Anina

    2017-01-01

    Background The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. Methods and Findings The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the

  16. Traumatic brain injury is unlikely precipitating Leigh syndrome due to the GJB2 mutation c.35delG

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2017-06-01

    Full Text Available With interest we read the article by Ashrafi et al. about a 14-year-old female who is regarded to have developed Leigh syndrome (LS after traumatic brain injury (TBI. We have the following comments and concerns:We do not agree with the notion that traumatic brain injury was the precipitating factor for LS. The patient had a history of hypoacusis, which is a typical clinical manifestation of a mitochondrial disorder (MID. Hypoacusis obviously had developed long before the TBI. Additionally, the patient was diagnosed with neuropathy of the peripheral nerves two months after TBI. It is rather unlikely that neuropathy was triggered by TBI and more likely it was already present before the trauma. Thus, the initial manifestations of LS in the presented patient were most likely hypoacusis followed by neuropathy and TBI only might have triggered the seizure but not the MID. Why was the patient put on phenytoin, which is well-known to be mitochondrion-toxic? Phenytoin may worsen epilepsy and MID in general and it is conceivable that in fact phenytoin was responsible for worsening of the phenotype and not the TBI. In a 16-year-old female with MELAS syndrome due to the mutation m.3243A>G, phenytoin caused intestinal pseudo-obstruction one month after intravenous phenytoin for status epilepticus. In a patient with Kearns-Sayre syndrome phenytoin decreased cerebrospinal fluid (CSF folate levels. In rat hepatocytes, phenytoin increased reactive oxygen species (ROS formation, decreased intracellular reduced glutathione, increased intracellular oxidised glutathione, and enhanced lipid peroxidation and mitochondrial damage. In a hepatic microsomal system, phenytoin decreased state-3 respiration, ATP synthesis, and the mitochondrial membrane potential. In this model, phenytoin increased state-4 respiration, impaired Ca++-uptake and release, and inhibited Ca++-induced swelling. It would be interesting to know how the GJB2 mutation was detected. Was whole exome or

  17. Fahr's Syndrome

    Science.gov (United States)

    ... from the National Library of Medicine’s MedlinePlus Genetic Brain Disorders Show More Show Less ... Definition Fahr's Syndrome is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of ...

  18. Gerstmann's Syndrome

    Science.gov (United States)

    ... drawings. Frequently, there is also an impairment in reading. Children with a high level of intellectual functioning as well as those with brain damage may be affected with the disorder. × Definition Gerstmann's syndrome is a cognitive impairment that results ...

  19. Paraneoplastic Syndromes

    Science.gov (United States)

    ... Division of Neuroscience Director, NIH BRAIN Initiative® Health Scientist Administrator Channels Synapses Circuits Cluster Scientific Director, Division of Intramural Research Featured Director's Message menu search Enter Search Term Submit Search Paraneoplastic Syndromes Information ...

  20. Antiphospholipid Syndrome

    Science.gov (United States)

    ... Division of Neuroscience Director, NIH BRAIN Initiative® Health Scientist Administrator Channels Synapses Circuits Cluster Scientific Director, Division of Intramural Research Featured Director's Message menu search Enter Search Term Submit Search Antiphospholipid Syndrome Information ...

  1. Angelman syndrome

    Science.gov (United States)

    ... the gene Other tests may include: Brain MRI EEG Treatment There is no cure for Angelman syndrome. ... nih.gov/pubmed/20301323 . Accessed August 1, 2015. Review Date 8/1/2015 Updated by: Chad Haldeman- ...

  2. Tourette Syndrome

    Science.gov (United States)

    ... Barré Syndrome Information Page Headache Information Page Hemicrania Continua Information Page Hemifacial Spasm Information Page Hereditary Spastic ... the Spotlight Find NINDS Clinical Trials Patient & Caregiver Education Fact Sheets Hope Through Research Know Your Brain ...

  3. The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

    Science.gov (United States)

    Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

    2016-04-01

    Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

  4. Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.

    Science.gov (United States)

    Lucke-Wold, Brandon P; Logsdon, Aric F; Turner, Ryan C; Rosen, Charles L; Huber, Jason D

    2014-01-01

    The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is third largest cause of mortality in the United States. The biggest risk factors for stroke, besides age, are results of the metabolic syndrome. The metabolic syndrome, if unchecked, quickly advances to outcomes that include diabetes, hypertension, cardiovascular disease, and obesity. The contribution from these comorbidities to BBB compromise is great. Some of the common molecular pathways activated include: endoplasmic reticulum stress, reactive oxygen species formation, and glutamate excitotoxicity. In this chapter, we examine how age-related changes to cells within the central nervous system interact with comorbidities. We then look at how comorbidities lead to increased risk for stroke through BBB disruption. Finally, we discuss key molecular pathways of interest with a focus on therapeutic targets that warrant further investigation. © 2014 Elsevier Inc. All rights reserved.

  5. A survey on the effects of Azithromycin in the treatment of gingival overgrowth induced by Cyclosporin in renal transplant patients

    Directory of Open Access Journals (Sweden)

    Kadkhoda Z.

    2004-07-01

    Full Text Available Statement of Problem: Gingival overgrowth is a side effect commonly induced by Cyclosporin treatment. The effects of Azithromycin, a macrolidic antibiotic, has been focused on gingival enlargement treatment induced by cyclosporine in numerous articles. Purpose: The goal of the present study was to survey the effects of systemic Azithromycin in the treatment of gingival overgrowth induced by cyclosporine among renal transplant patients. Materials and Methods: In this clinical trial study, 18 renal transplant patients (6 females and 12 males with gingival overgrowth were studied. Samples were randomly divided into two groups: case group were treated by systemic Azithromycin and controls were treated by systemic placebo. Periodontal parameters including bleeding on probing (BOP, clinical crown length (CL, periodontal pocket depth (PPD, gingival overgrowth (GOI and stent-IDP (vertical distant between a stent or plate with teeth occlusal planes at least from three of the most anterior contact points to mesial papillae before treatment, two and six weeks after treatment were measured. To analyze the data, Wilcoxon and Mann-Whitney tests were used. Results: Most of the measured indices, among case and control groups, were significantly improved, after two weeks (P<0.05. No statistically significant differences were found between two groups except for BOP index (P<0.05. In other words, more BOP improvement was observed in the case group after six weeks comparing to the control group. Conclusion: Considering the findings of this study, one can assume that the reported effects of Azithromycine on gingival overgrowth, induced by cyclosporine is somehow exaggerated and the effects attributed this medicine is probably inflammation reduction.

  6. Melatonin alterations and brain acetylcholine lesions in sleep disorders in Cockayne syndrome.

    Science.gov (United States)

    Okoshi, Yumi; Tanuma, Naoyuki; Miyata, Rie; Hayashi, Masaharu

    2014-11-01

    Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. Sleep-wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  7. Dysregulation of heart and brain specific micro-RNA in sudden infant death syndrome.

    Science.gov (United States)

    Courts, Cornelius; Grabmüller, Melanie; Madea, Burkhard

    2013-05-10

    Channelopathic heart arrhythmias and dysfunctional autonomic regulation of respiration and arousal based on defects in the brainstem are assumed to be involved in the pathogenesis of SIDS. There is evidence that, apart from mutational alterations in associated genes, disruption of physiological processes and deficient responses to external stressors may be influenced by the dysregulation of organ specific micro-RNA expression. It is unknown, however, whether these small, non-coding regulatory RNA molecules are involved in any SIDS pathomechanism. In a case-control study of two series of fresh-frozen heart tissue (n=14) and formalin fixed, paraffin embedded brainstem tissue (n=11) from SIDS and respective control cases, differential expression of heart and brain specific miR-1/miR-133 and miR-124a/let-7b, respectively, was determined using quantitative PCR analysis. Our results show a significant upregulation of heart specific miR-1 and brainspecific let-7b in SIDS compared to control cases. This pilot study is first to analyze differential miRNA expression in SIDS. Our findings suggest that organ specific miRNA dysregulation may be associated with SIDS pathogenesis and establishes the feasibility of miRNA analysis in different kinds of preserved and archived SIDS tissues. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain.

    Science.gov (United States)

    Perluigi, Marzia; Pupo, Gilda; Tramutola, Antonella; Cini, Chiara; Coccia, Raffaella; Barone, Eugenio; Head, Elizabeth; Butterfield, D Allan; Di Domenico, Fabio

    2014-07-01

    Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aβ) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3β activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B

    Science.gov (United States)

    Handen, Benjamin L.; Cohen, Ann D.; Channamalappa, Umapathy; Bulova, Peter; Cannon, Sheila A.; Cohen, William I.; Mathis, Chester A.; Price, Julie C.; Klunk, William E.

    2012-01-01

    Down syndrome (DS) is one of the most common causes of intellectual disability. Although DS accounts for only 15% of all individuals with intellectual disabilities, adults with DS account for approximately 60% of individuals with intellectual disabilities and Alzheimer’s disease. This is thought to be because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. Pittsburgh compound B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer’s disease also show preclinical amyloid deposition. This report describes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with objective cutoffs for amyloid positivity in older non-DS cognitively normal control subjects, only two of the seven DS subjects (age: 38 and 44 years) showed increased PiB retention. The remaining five subjects aged between 20 and 35 years showed no detectable increase in PiB retention. Interestingly, the two subjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasibility of conducting PiB positron emission tomography scanning in this special population, and suggest a link between Aβ overproduction and early striatal deposition of fibrillar Aβ. PMID:23102120

  10. The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome.

    Science.gov (United States)

    Miyake, Kunio; Hirasawa, Takae; Soutome, Masaki; Itoh, Masayuki; Goto, Yu-ichi; Endoh, Kazushi; Takahashi, Kenichiro; Kudo, Shinichi; Nakagawa, Takayuki; Yokoi, Sana; Taira, Takahiro; Inazawa, Johji; Kubota, Takeo

    2011-08-08

    Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of Methyl-CpG-binding protein 2 (MECP2) gene. MeCP2 protein is mainly expressed in neurons and binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes in neurons. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT. Using a genome-microarray approach, we found 22 genomic regions that contain sites potentially regulated by MeCP2 based on the features of MeCP2 binding, DNA methylation, and repressive histone modification in human cell lines. Within these regions, Chromatin immunoprecipitation (ChIP) analysis revealed that MeCP2 binds to the upstream regions of the protocadherin genes PCDHB1 and PCDH7 in human neuroblastoma SH-SY5Y cells. PCDHB1 and PCDH7 promoter activities were down-regulated by MeCP2, but not by MBD-deleted MeCP2. These gene expression were up-regulated following MeCP2 reduction with siRNA in SH-SY5Y cells and in the brains of Mecp2-null mice. Furthermore, PCDHB1 was up-regulated in postmortem brains from Rett syndrome patients. We identified MeCP2 target genes that encode neuronal adhesion molecules using ChIP-on-BAC array approach. Since these protocadherin genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.

  11. The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Nakagawa Takayuki

    2011-08-01

    Full Text Available Abstract Background Rett syndrome is a neurodevelopmental and autistic disease caused by mutations of Methyl-CpG-binding protein 2 (MECP2 gene. MeCP2 protein is mainly expressed in neurons and binds to methylated gene promoters to suppress their expression, indicating that Rett syndrome is caused by the deregulation of target genes in neurons. However, it is likely that there are more unidentified neuronal MeCP2-targets associated with the neurological features of RTT. Results Using a genome-microarray approach, we found 22 genomic regions that contain sites potentially regulated by MeCP2 based on the features of MeCP2 binding, DNA methylation, and repressive histone modification in human cell lines. Within these regions, Chromatin immunoprecipitation (ChIP analysis revealed that MeCP2 binds to the upstream regions of the protocadherin genes PCDHB1 and PCDH7 in human neuroblastoma SH-SY5Y cells. PCDHB1 and PCDH7 promoter activities were down-regulated by MeCP2, but not by MBD-deleted MeCP2. These gene expression were up-regulated following MeCP2 reduction with siRNA in SH-SY5Y cells and in the brains of Mecp2-null mice. Furthermore, PCDHB1 was up-regulated in postmortem brains from Rett syndrome patients. Conclusions We identified MeCP2 target genes that encode neuronal adhesion molecules using ChIP-on-BAC array approach. Since these protocadherin genes are generally essential for brain development, aberrant regulation of these molecules may contribute to the pathogenesis of the neurological features observed in Rett syndrome.

  12. Influence of the Prader-Willi syndrome imprinting center on the DNA methylation landscape in the mouse brain.

    Science.gov (United States)

    Brant, Jason O; Riva, Alberto; Resnick, James L; Yang, Thomas P

    2014-11-01

    Reduced representation bisulfite sequencing (RRBS) was used to analyze DNA methylation patterns across the mouse brain genome in mice carrying a deletion of the Prader-Willi syndrome imprinting center (PWS-IC) on either the maternally- or paternally-inherited chromosome. Within the ~3.7 Mb imprinted Angelman/Prader-Willi syndrome (AS/PWS) domain, 254 CpG sites were interrogated for changes in methylation due to PWS-IC deletion. Paternally-inherited deletion of the PWS-IC increased methylation levels ~2-fold at each CpG site (compared to wild-type controls) at differentially methylated regions (DMRs) associated with 5' CpG island promoters of paternally-expressed genes; these methylation changes extended, to a variable degree, into the adjacent CpG island shores. Maternal PWS-IC deletion yielded little or no changes in methylation at these DMRs, and methylation of CpG sites outside of promoter DMRs also was unchanged upon maternal or paternal PWS-IC deletion. Using stringent ascertainment criteria, ~750,000 additional CpG sites were also interrogated across the entire mouse genome. This analysis identified 26 loci outside of the imprinted AS/PWS domain showing altered DNA methylation levels of ≥25% upon PWS-IC deletion. Curiously, altered methylation at 9 of these loci was a consequence of maternal PWS-IC deletion (maternal PWS-IC deletion by itself is not known to be associated with a phenotype in either humans or mice), and 10 of these loci exhibited the same changes in methylation irrespective of the parental origin of the PWS-IC deletion. These results suggest that the PWS-IC may affect DNA methylation at these loci by directly interacting with them, or may affect methylation at these loci through indirect downstream effects due to PWS-IC deletion. They further suggest the PWS-IC may have a previously uncharacterized function outside of the imprinted AS/PWS domain.

  13. Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis.

    Science.gov (United States)

    Sacco, Roberto; Gabriele, Stefano; Persico, Antonio M

    2015-11-30

    Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Effects of postnatal dietary choline supplementation on motor regional brain volume and growth factor expression in a mouse model of Rett syndrome.

    Science.gov (United States)

    Nag, Nupur; Mellott, Tiffany J; Berger-Sweeney, Joanne E

    2008-10-27

    Nutritional status during pregnancy and lactation can influence behavioral and anatomical characteristics of several neurological disorders in the offspring, including Rett syndrome (RTT). RTT is associated with mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCp2), a transcriptional repressor that binds methylated DNA. In Mecp2(1lox) mice, a model of RTT, enhancing maternal nutrition through choline supplementation attenuates motor coordination deficits in the mutant offspring. Here, we examine alterations in brain volume and growth factor expression in the cerebellum and striatum, motor regions that may contribute to the improved behavioral performance seen with choline supplementation. Mecp2(1lox) dams were given choline in drinking water, and pups nursed from birth to weaning. Brains of male offspring were collected at postnatal day 42 for volumetric and growth factor expression analyses. Compared to wild-type mice, Mecp2(1lox) null mice had decreased whole brain, cerebellar and striatal volume. Choline supplementation had no effect on brain volume. Nerve growth factor and insulin-like growth factor-1 expression was similar between wild-type and Mecp2(1lox) mice while brain derived neurotrophic factor was reduced in Mecp2(1lox) mice. Choline supplementation increased striatal nerve growth factor expression in wild-type and Mecp2(1lox) mice, suggesting that neuronal proliferation and survival may contribute to improved motor performance in this model of RTT.

  15. Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome

    Science.gov (United States)

    Bueno, Marta; Esteba-Castillo, Susanna; Novell, Ramon; Giménez-Palop, Olga; Coronas, Ramon; Gabau, Elisabeth; Corripio, Raquel; Baena, Neus; Viñas-Jornet, Marina; Guitart, Míriam; Torrents-Rodas, David; Deus, Joan; Pujol, Jesús; Rigla, Mercedes

    2016-01-01

    Context Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. Objectives To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. Design Experimental study. Setting University hospital. Subjects 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. Interventions Subjects ingested a liquid meal after fasting ≥10 hours. Main Outcome Measures Leptin and BDNF levels in plasma extracted before ingestion and 30’, 60’, and 120’ after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60’ and 120’ after ingestion. Results Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65–0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13–0.9). Postprandial leptin patterns did no differ among genetic subtypes. Conclusions Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors. PMID:27685845

  16. Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease.

    Science.gov (United States)

    Di Domenico, Fabio; Pupo, Gilda; Tramutola, Antonella; Giorgi, Alessandra; Schininà, Maria Eugenia; Coccia, Raffaella; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

    2014-06-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21. DS subjects are characterized by a number of abnormalities including premature aging and development of Alzheimer disease (AD) neuropathology after approximately 40 years of age. Several studies show that oxidative stress plays a crucial role in the development of neurodegeneration in the DS population. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipids, and proteins. In this study we used a redox proteomics approach to identify specific targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases with and without AD pathology. We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD. The third group of comparison, DS/AD vs old controls, identified proteins that may be considered specific markers of AD pathology. All the identified proteins are involved in important biological functions including intracellular quality control systems, cytoskeleton network, energy metabolism, and antioxidant response. Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development. Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Deep Brain Stimulation in Gilles de la Tourette Syndrome: What Does the Future Hold? A Cohort of 48 Patients.

    Science.gov (United States)

    Servello, Domenico; Zekaj, Edvin; Saleh, Christian; Lange, Nicholas; Porta, Mauro

    2016-01-01

    Gilles de la Tourette syndrome (GTS) is a severe neuropsychiatric disorder with childhood onset, characterized by disabling motor and vocal tics lasting for more than 1 year and associated with a wide range of psychiatric comorbidities. Pharmacological treatment is indicated for moderate to severe GTS patients. However, when GTS is refractory to conventional medical and behavioral treatments, deep brain stimulation (DBS) can be considered as a last resort therapeutic avenue. To evaluate the efficacy of DBS and its comorbidities in the largest pool of GTS patients to date. Our cohort study was based on 48 patients' refractory to conventional treatment who underwent DBS for GTS at Galeazzi Institute, Milan, Italy. An exhaustive preoperative and a follow-up battery of tests was performed including the Yale Global Tic Severity Rating Scale, the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Subjective Social Impairment on a 10-point Visual Analogue Scale tests. Eleven patients in whom the device was removed for inflammatory complications or for poor compliance were excluded from final analysis. Twenty-seven of the remaining 37 patients had a Yale Global Tic Severity Rating Scale score at the last follow-up that was less than 35. Of the 37 patients, in 29 cases (78%) a reduction of more than 50% of the Yale Global Tic Severity Rating Scale score was observed. The clinical efficacy of DBS in GTS is promising. Although DBS is associated with risks, as is any surgical intervention, DBS should be considered as a last resort therapeutic option in carefully selected GTS patients.

  18. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    Directory of Open Access Journals (Sweden)

    Elena Lima-Cabello

    2016-01-01

    Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  19. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.

    Science.gov (United States)

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes; de Diego-Otero, Yolanda

    2016-01-01

    Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

  20. Sotos syndrome

    Directory of Open Access Journals (Sweden)

    Cormier-Daire Valérie

    2007-09-01

    Full Text Available Abstract Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC, advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (

  1. A genetic screen in Drosophila implicates Sex comb on midleg (Scm) in tissue overgrowth and mechanisms of Scm degradation by Wds.

    Science.gov (United States)

    Guo, Jiwei; Jin, Dan

    2015-05-01

    The sex comb on midleg (scm) gene encodes a transcriptional repressor and belongs to the Polycomb group (PcG) of genes, which regulates growth in Drosophila. Scm interacts with Polyhomeotic (a PcG protein) in vitro by recognizing its SPM domain. The homologous human protein, Sex comb on midleg-like 2 (Scml2), has been implicated in malignant brain tumors. Will die slowly (Wds) is another factor that regulates Drosophila development, and its homologous human protein, WD repeat domain 5(Wdr5), is part of the mixed lineage leukemia 1(MLL1) complex that promotes histone H3Lys4 methylation. Like Scml2, Wdr5 has been implicated in certain cancers; this protein plays an important role in leukemogenesis. In this study, we find that loss-of-function mutations in Scm result in non-autonomous tissue overgrowth in Drosophila, and determine that Scm is essential for ommatidium development and important for cell survival in Drosophila. Furthermore, our research suggests a relationship between Wds and Scm; Wds promotes Scm degradation through ubiquitination in vitro in Drosophila. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Asymmetric Pectus Excavatum Is Associated with Overgrowth of Ribs Rather Than Cartilage.

    Science.gov (United States)

    Park, Chul Hwan; Kim, Tae Hoon; Haam, Seok Jin; Lee, Sungsoo

    2015-08-01

    To evaluate whether the overgrowth of costal cartilage exists in patients with pectus excavatum, we compared the length of the costal cartilage and ribs between patients with asymmetric pectus excavatum and controls without chest wall deformity using three-dimensional computed tomography. Nineteen adult patients with asymmetric pectus excavatum and 19 age and sex matched controls without chest wall deformity were enrolled. We measured the full lengths of the fourth to sixth ribs and costal cartilage using three-dimensional volume-rendered computed tomography images and curved multiplanar reformatting techniques. The lengths of ribs and costal cartilage, their summations, and the costal index ([length of cartilage/length of rib] × 100 [%]) were compared on the asymmetrically depressed side of patients (Group A), the opposite side of the same patients (Group B), and controls (Group C) at the fourth to sixth levels. The lengths of the ribs of groups A and B were significantly longer (p  0.05) among the three groups (53.1 ± 7.3 mm vs. 54.6 ± 8.6 mm vs. 52.9 ± 5.2 at the fourth level, 71.9 ± 9.6 mm vs. 72.3 ± 9.9 mm vs. 69.2 ± 7.1 mm at the fifth level, and 100.1 ± 15.2 mm vs. 104.2 ± 15.8 mm vs. 99.1 ± 9.1 mm at sixth level). The summations of the rib and costal cartilage lengths were longer in groups A and B than in group C. The costal indices were not different among the three groups at the fourth, fifth, and sixth rib levels. In patients who had asymmetric pectus excavatum with a ≥ 21-degree angle of sternal rotations, the ribs but not the costal cartilage were longer than those of controls. These findings suggest that cartilage overgrowth is not the main factor responsible for asymmetric pectus excavatum, and it could instead be related to abnormal rib growth. Georg Thieme Verlag KG Stuttgart · New York.

  3. Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Magraner, Maria Jose; Bosca, Isabel; Simo-Castello, Maria; Casanova, Bonaventura [Hospital La Fe, Multiple Sclerosis Unit, Neurology Department, Valencia (Spain); Garcia-Marti, Gracian [Hospital Quiron, Magnetic Resonance Unit, Valencia (Spain); CIBER Mental Health Network, ISCIII, Valencia (Spain); Alberich-Bayarri, Angel; Marti-Bonmati, Luis [Hospital Quiron, Magnetic Resonance Unit, Valencia (Spain); Coret, Francisco [Hospital Clinic Universitari, Multiple Sclerosis Unit, Neurology Department, Valencia (Spain); Alvarez-Cermeno, Jose C. [Hospital Ramon y Cajal, Neurology Department, Madrid (Spain); Villar, Luisa M. [Hospital Ramon y Cajal, Immunology Department, Madrid (Spain)

    2012-01-15

    The objective of this work is to study the relationship between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in CSF, with both T2 lesion volume (T2LV) accumulation and brain atrophy (percentage change of brain volume-PCBV-and brain parenchyma fraction-BPF) in patients with clinically isolated syndromes (CIS) suggestive of demyelination. Twenty-four CIS patients were included in this prospective study. IgG oligoclonal bands (OCGB) and LS-OCMB were determined in paired serum and CSF samples within 3 months since clinical onset. Brain MRI studies were scheduled at baseline, 3 months, first and second years after CIS onset. Differences in T2LV, PCBV and BPF between CIS patients according to the type of OCB were studied. Nine patients had no OCB; 15 had only OCGB, and seven had OCGB + LS-OCMB present in the CSF. LS-OCMB were associated with greater T2LV in all scheduled MRI studies. At the end of follow-up (year 2), it was threefold higher in patients with these antibodies than in those without LS-OCMB (3.95 cm{sup 3} vs. 1.36 cm{sup 3}, p = 0.001). At that point, brain atrophy was also higher in patients with LS-OCMB (BPF, 0.73 in LS-OCMB+ patients vs. 0.76 in negative ones, p = 0.03). The rate in brain atrophy was higher in the first group of patients as well. Considering only patients with OCGB, the presence of LS-OCMB was also related to greater T2LV, T2LV increase and a trend towards higher atrophy rate. The presence of LS-OCMB in the first event suggestive of demyelination is related to an early increase in lesion load and brain atrophy. These data are in line with prospective studies showing the clinical prognostic value of LS-OCMB. (orig.)

  4. Guillain-Barre Syndrome

    Science.gov (United States)

    Guillain-Barre syndrome is a rare disorder that causes your immune system to attack your peripheral nervous system (PNS). The PNS ... your brain. No one knows what causes the syndrome. Sometimes it is triggered by an infection, surgery, ...

  5. Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy.

    Science.gov (United States)

    Domann, Eugen; Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A

    2016-07-28

    d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. Copyright © 2016 Domann et al.

  6. Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions

    NARCIS (Netherlands)

    Mutsaers, Henricus A M; Levtchenko, Elena N; Martinerie, Laetitia; Pertijs, Jeanne C L M; Allegaert, Karel; Devriendt, Koenraad; Masereeuw, Roos; Monnens, Leo A H; Lombès, Marc

    CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile

  7. Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions

    NARCIS (Netherlands)

    Mutsaers, H.A.M.; Levtchenko, E.N.; Martinerie, L.; Pertijs, J.C.L.M.; Allegaert, K.; Devriendt, K.; Masereeuw, R.; Monnens, L.A.; Lombes, M.

    2014-01-01

    CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic spectrum including overgrowth and learning difficulties. Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile

  8. Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann syndrome due to defects in the function of pancreatic beta-cell adenosine triphosphate-sensitive potassium channels

    DEFF Research Database (Denmark)

    Hussain, K; Cosgrove, K E; Shepherd, R M

    2005-01-01

    Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is clinically and genetically heterogeneous. Hyperinsulinemic hypoglycemia occurs in about 50% of children with BWS and, in the majority of infants, it resolves spontaneously. However, in a small group of patients the hypo...

  9. Distinct Effects of Allelic NFIX Mutations on Nonsense-Mediated mRNA Decay Engender Either a Sotos-like or a Marshall-Smith Syndrome

    Science.gov (United States)

    Malan, Valérie; Rajan, Diana; Thomas, Sophie; Shaw, Adam C.; Louis dit Picard, Hélène; Layet, Valérie; Till, Marianne; van Haeringen, Arie; Mortier, Geert; Nampoothiri, Sheela; Pušeljić, Silvija; Legeai-Mallet, Laurence; Carter, Nigel P.; Vekemans, Michel; Munnich, Arnold; Hennekam, Raoul C.; Colleaux, Laurence; Cormier-Daire, Valérie

    2010-01-01

    By using a combination of array comparative genomic hybridization and a candidate gene approach, we identified nuclear factor I/X (NFIX) deletions or nonsense mutation in three sporadic cases of a Sotos-like overgrowth syndrome with advanced bone age, macrocephaly, developmental delay, scoliosis, and unusual facies. Unlike the aforementioned human syndrome, Nfix-deficient mice are unable to gain weight and die in the first 3 postnatal weeks, while they also present with a spinal deformation and decreased bone mineralization. These features prompted us to consider NFIX as a candidate gene for Marshall-Smith syndrome (MSS), a severe malformation syndrome characterized by failure to thrive, respiratory insufficiency, accelerated osseous maturation, kyphoscoliosis, osteopenia, and unusual facies. Distinct frameshift and splice NFIX mutations that escaped nonsense-mediated mRNA decay (NMD) were identified in nine MSS subjects. NFIX belongs to the Nuclear factor one (NFI) family of transcription factors, but its specific function is presently unknown. We demonstrate that NFIX is normally expressed prenatally during human brain development and skeletogenesis. These findings demonstrate that allelic NFIX mutations trigger distinct phenotypes, depending specifically on their impact on NMD. PMID:20673863

  10. Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: alternative definition and further delineation of MOMO syndrome.

    Science.gov (United States)

    Di Donato, N; Riess, A; Hackmann, K; Rump, A; Huebner, A; von der Hagen, M; Hahn, G; Schrock, E; Tinschert, S

    2012-11-01

    MOMO syndrome, previously defined as Macrosomia, Obesity, Macrocephaly, and Ocular abnormalities (OMIM 157980) is a rare intellectual disability syndrome of unknown cause. We describe two further patients with MOMO syndrome. Reported data of patients with MOMO syndrome and our own findings indicate that overgrowth does not appear to be a specific feature. We propose to form the acronym "MOMO" from Macrocephaly, Obesity, Mental (intellectual) disability, and Ocular abnormalities, excluding macrosomia from the syndrome name. The combination of obesity, macrocephaly, and colobomas is unique, therefore these features can be used as major diagnostic criteria of MOMO syndrome. Copyright © 2012 Wiley Periodicals, Inc.

  11. MBE overgrowth of ex-situ prepared CdSe colloidal nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Paluga, M.; Pawlis, A.; Lischka, K.; Schikora, D. [Department Physik, Universitaet Paderborn, Warburger Str. 100, 33098 Paderborn (Germany); Artemyev, M.V. [Institute for Physico-Chemical Problems of Belarussian State University, Minsk 220030 (Belarus); Woggon, U. [Technische Universitaet Berlin, Institut fuer Optik und Atomare Physik, Strasse des 17. Juni 135, 10623 Berlin (Germany); Rashad, M.

    2010-06-15

    We present a growth technique, which combines molecular beam epitaxy of ZnSe and externally wet-chemically prepared, colloidal NCs of CdSe to achieve fully integrated monolithic epitaxial heterostructures. Our results show that wet-chemically prepared semiconductor nanocrystals can be incorporated in an epitaxially grown crystalline cap layer. We investigated CdSe core, CdSe/ZnSe and CdSe/ZnS core/shell nanocrystals (NCs) overgrown with cap layers of ZnSe, where the thickness was varied between 20-40 nm. In this paper we discuss PL measurements of overgrown NCs as a function of the cap layer thickness and compare the results with the PL of NCs in solution. A distinct blue shift of the PL is observed when the core/shell dots are overgrown by ZnSe. We present a model which explains this blue shift as resulting from dissolution of the shell of the dots during the overgrowth (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  12. Prevalence of Small Intestinal Bacterial Overgrowth among Chronic Pancreatitis Patients: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Amelie Therrien

    2016-01-01

    Full Text Available Background. Patients with chronic pancreatitis (CP exhibit numerous risk factors for the development of small intestinal bacterial overgrowth (SIBO. Objective. To determine the prevalence of SIBO in patients with CP. Methods. Prospective, single-centre case-control study conducted between January and September 2013. Inclusion criteria were age 18 to 75 years and clinical and radiological diagnosis of CP. Exclusion criteria included history of gastric, pancreatic, or intestinal surgery or significant clinical gastroparesis. SIBO was detected using a standard lactulose breath test (LBT. A healthy control group also underwent LBT. Results. Thirty-one patients and 40 controls were included. The patient group was significantly older (53.8 versus 38.7 years; P < 0.01. The proportion of positive LBTs was significantly higher in CP patients (38.7 versus 2.5%: P < 0.01. A trend toward a higher proportion of positive LBTs in women compared with men was observed (66.6 versus 27.3%; P = 0.056. The subgroups with positive and negative LBTs were comparable in demographic and clinical characteristics, use of opiates, pancreatic enzymes replacement therapy (PERT, and severity of symptoms. Conclusion. The prevalence of SIBO detected using LBT was high among patients with CP. There was no association between clinical features and the risk for SIBO.

  13. Small bowel bacterial overgrowth may not affect bone mineral density in older people.

    Science.gov (United States)

    Mitsui, Takahiro; Shimaoka, Kiyoshi; Takagi, Chihiro; Goto, Yumi; Kagami, Hideo; Ito, Akira

    2005-12-01

    Small bowel bacterial overgrowth (SBBO) may be associated with malnutrition, diarrhea, and weight loss. Recently, bone mineral density (BMD) in patients with SBBO was reported to be lower, and SBBO may be an important factor in the development of metabolic bone disease. However, the subjects in these studies were relatively young patients with intestinal diseases. There is no information on the effect of SBBO on BMD in older people. Seventeen relatively active and 33 disabled older people participated in this study. SBBO was determined by a breath hydrogen (H2) test after ingestion of a glucose solution. BMD of the lumbar spine and femur were measured using a dual energy X-ray absorptiometry scan (DEXA). One healthy control and 11 disabled subjects were SBBO-positive. The Z-scores of the lumbar spine were not statistically different between groups, and a high incidence of disorders, >70%, was seen in all groups. On the other hand, there were significant differences in the femoral BMD between the healthy controls and the SBBO-negative (Pinstitutionalized people. SBBO seems to have little effect on BMD in people approximately 80 years old.

  14. Small intestinal bacterial overgrowth in inactive Crohn’s disease: Influence of thiopurine and biological treatment

    Science.gov (United States)

    Sánchez-Montes, Cristina; Ortiz, Vicente; Bastida, Guillermo; Rodríguez, Ester; Yago, María; Beltrán, Belén; Aguas, Mariam; Iborra, Marisa; Garrigues, Vicente; Ponce, Julio; Nos, Pilar

    2014-01-01

    AIM: To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn’s disease (CD). METHODS: This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. RESULTS: One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P meteorism and a fistulizing pattern were associated with the presence of SIBO (P meteorism are associated with SIBO. PMID:25320539

  15. Small intestinal bacterial overgrowth in inactive Crohn's disease: influence of thiopurine and biological treatment.

    Science.gov (United States)

    Sánchez-Montes, Cristina; Ortiz, Vicente; Bastida, Guillermo; Rodríguez, Ester; Yago, María; Beltrán, Belén; Aguas, Mariam; Iborra, Marisa; Garrigues, Vicente; Ponce, Julio; Nos, Pilar

    2014-10-14

    To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn's disease (CD). This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P meteorism and a fistulizing pattern were associated with the presence of SIBO (P meteorism are associated with SIBO.

  16. Heat resistive dielectric multi-layer micro-mirror array in epitaxial lateral overgrowth gallium nitride.

    Science.gov (United States)

    Huang, Chen-Yang; Ku, Hao-Min; Liao, Wei-Tsai; Chao, Chu-Li; Tsay, Jenq-Dar; Chao, Shiuh

    2009-03-30

    Ta2O5 / SiO2 dielectric multi-layer micro-mirror array (MMA) with 3mm mirror size and 6mm array period was fabricated on c-plane sapphire substrate. The MMA was subjected to 1200 degrees C high temperature annealing and remained intact with high reflectance in contrast to the continuous multi-layer for which the layers have undergone severe damage by 1200 degrees C annealing. Epitaxial lateral overgrowth (ELO) of gallium nitride (GaN) was applied to the MMA that was deposited on both sapphire and sapphire with 2:56 mm GaN template. The MMA was fully embedded in the ELO GaN and remained intact. The result implies that our MMA is compatible to the high temperature growth environment of GaN and the MMA could be incorporated into the structure of the micro-LED array as a one to one micro backlight reflector, or as the patterned structure on the large area LED for controlling the output light.

  17. Single-crystal silicon beams formed by merged epitaxial lateral overgrowth (MELO) for optical reflectors

    Science.gov (United States)

    Neudeck, Gerold W.; Kabir, Abul E.

    1995-05-01

    Single crystalline silicon has very well known and predictable mechanical, optical, and electrical properties and is easily manufactured with consistent results. It is also integrated circuit compatible and leads to incorporation of circuits and high quality piezoresistors which are available to monitor motion for self-testing. We present for the first time a novel surface micro-machining process using merged epitaxial lateral overgrowth (MELO) silicon to demonstrate the fabrication of single crystal silicon, free standing cantilever beams 1 mm long and 5 micrometers X 10 micrometers in cross section. These beams had no evidence of stress related bending and were free from the substrate, returning to its original position after numerous electrostatic deflections. MELO has also shown great potential for advanced BJT and MOSFET device applications, hence active devices can be incorporated into the deflecting beam arrays. Diodes fabricated in the beams show excellent characteristics with average ideality factors of 1.01. Note that the technology permits adding of single crystal silicon to selected areas, hence it is an additive process as compared to traditional subtractive methods that deposit films over the entire wafer.

  18. Effect of probiotics on small intestinal bacterial overgrowth in patients with gastric and colorectal cancer.

    Science.gov (United States)

    Liang, Sufang; Xu, Lin; Zhang, Dongsheng; Wu, Zhenjun

    2016-05-01

    Small intestinal bacterial overgrowth (SIBO) may be related to the presence of gastrointestinal cancer. The exact link, however, between SIBO and cancer prevalence as well as cancer symptoms remains unclear, especially in Asian populations. In addition, there is a paucity of data documenting the influence of probiotic treatment of SIBO on cancer symptoms. Here, the aims were to correlate the presence of SIBO with cancer prevalence and cancer symptoms, as well as to investigate the effect of probiotic intervention on SIBO and cancer symptoms. Employing a case-control design, 112 gastric and 88 colorectal cancer patients were evaluated. Questionnaires were used to assess gastrointestinal symptoms and a glucose-H2-breath test (GHBT) was used to determine SIBO status. Patients with SIBO were administered Bifidobacterium triple viable capsule therapy or placebo. Subsequently, SIBO status and gastrointestinal symptom scores were reanalyzed. In our study group, 63.0% of patients versus 16.3% of controls was tested positive for SIBO. In patients with cancer, SIBO was associated with proton pump inhibitor (PPI) use. Bifidobacterium triple viable capsule was effective in combating SIBO and was associated with a significant improvement in gastrointestinal cancer-related symptoms. In a Chinese cohort, SIBO is associated with gastrointestinal cancer. Based on the preliminary intervention study, we conclude that probiotic intervention combats SIBO in patients with gastrointestinal cancer and alleviates its symptoms.

  19. Doom and boom on a resilient reef: climate change, algal overgrowth and coral recovery.

    Science.gov (United States)

    Diaz-Pulido, Guillermo; McCook, Laurence J; Dove, Sophie; Berkelmans, Ray; Roff, George; Kline, David I; Weeks, Scarla; Evans, Richard D; Williamson, David H; Hoegh-Guldberg, Ove

    2009-01-01

    Coral reefs around the world are experiencing large-scale degradation, largely due to global climate change, overfishing, diseases and eutrophication. Climate change models suggest increasing frequency and severity of warming-induced coral bleaching events, with consequent increases in coral mortality and algal overgrowth. Critically, the recovery of damaged reefs will depend on the reversibility of seaweed blooms, generally considered to depend on grazing of the seaweed, and replenishment of corals by larvae that successfully recruit to damaged reefs. These processes usually take years to decades to bring a reef back to coral dominance. In 2006, mass bleaching of corals on inshore reefs of the Great Barrier Reef caused high coral mortality. Here we show that this coral mortality was followed by an unprecedented bloom of a single species of unpalatable seaweed (Lobophora variegata), colonizing dead coral skeletons, but that corals on these reefs recovered dramatically, in less than a year. Unexpectedly, this rapid reversal did not involve reestablishment of corals by recruitment of coral larvae, as often assumed, but depended on several ecological mechanisms previously underestimated. These mechanisms of ecological recovery included rapid regeneration rates of remnant coral tissue, very high competitive ability of the corals allowing them to out-compete the seaweed, a natural seasonal decline in the particular species of dominant seaweed, and an effective marine protected area system. Our study provides a key example of the doom and boom of a highly resilient reef, and new insights into the variability and mechanisms of reef resilience under rapid climate change.

  20. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.

    LENUS (Irish Health Repository)

    Shanab, Ahmed Abu

    2011-05-01

    Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).

  1. Anesthetic Management of a 12-Year-Old Patient with Proteus Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Kilic

    2014-06-01

    Full Text Available Proteus syndrome is an exceptionally rare congenital disorder with asymmetrical disproportionate overgrowth that includes any tissue of the body. Most of the patients with Proteus syndrome are generally needed to operate for overgrowths and related deformities. However, pulmonary manifestations such as cystic lung and vertebral abnormalities including kyphoscoliosis can lead to high anesthesia risk. The patients with Proteus syndrome should be evaluated in detail preoperatively, and managed carefully during and after anesthesia. Although up to 200 cases with Proteus syndrome have been reported to date, there are few reports on anesthetic management in such cases. In this paper, we present a Proteus syndrome in a case of 12-year old boy who was succesfully operated for foot reconstruction without any anesthesia-related complication.

  2. Prenatal sonographic diagnosis of Beckwith-Wiedemann syndrome in association with a single umbilical artery.

    Science.gov (United States)

    Hamada, H; Fujiki, Y; Obata-Yasuoka, M; Watanabe, H; Yamada, N; Kubo, T

    2001-01-01

    Beckwith-Wiedemann syndrome is an inherited disorder most commonly characterized by prenatal or postnatal overgrowth, macroglossia, omphalocele, unusual earlobe creases, and increased risk of neoplasia. Several reported cases of this syndrome have been prenatally diagnosed, but no report has described the occurrence of this syndrome in association with a single umbilical artery. We report a case in which prenatal sonographic examination demonstrated fetal overgrowth, macroglossia, and omphalocele together with a single umbilical artery; our prenatal diagnosis of Beckwith-Wiedemann syndrome was confirmed after birth of the infant. The possibility of this syndrome should be considered when performing a detailed sonographic examination of a fetus with a single umbilical artery. Copyright 2001 John Wiley & Sons, Inc.

  3. DOWN SYNDROME WITH MOYAMOYA SYNDROME

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    Mohan Makwana

    2017-04-01

    Full Text Available BACKGROUND Moyamoya disease is a disorder of blood vessels in the brain, specifically the internal carotid arteries and the arteries that branch from them. The primary idiopathic form “moyamoya disease” has been distinguished from an associated form of “moyamoya syndrome,” in which the arterial changes are seen among patients with various syndromes or other disease processes- Down syndrome, sickle cell anaemia, neurofibromatosis type-1, congenital heart disease, fibromuscular dysplasia, activated protein C resistance, or head trauma. There have been only 47 previous cases of moyamoya syndrome in association with Down syndrome reported in the world literature. Recently, we have come across a Case of Downs’ Syndrome with Moyamoya Syndrome. Because of its rarity we want to report our case.

  4. Regional Cerebral Blood-Flow with 99mTc-ECD Brain Perfusion SPECT in Landau-Kleffner Syndrome: Report of Two Cases

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    Reza Nemati

    2014-01-01

    Full Text Available Landau-Kleffner syndrome (LKS is a rare childhood disorder characterized by acquired aphasia and epilepsy. 99mTc-ECD SPECT imaging was performed in two right-handed children with LKS. A relative decrease in perfusion was found in the left frontal-temporal cortices of both patients as well as in the left and right parietal cortices of one patient with aphasia, without clinical epilepsy. The degree of regional cerebral perfusion impairment did not correlate with the severity of the clinical and EEG abnormalities, but the area of hypoperfusion was compatible with the speech area of the brain. Overall, although asymmetrical temporoparietal perfusion appears as a common finding in LKS, SPECT findings in LKS alone cannot elucidate the pathogenic features of the disorder in the brain. Here, we present two cases of LKS in which we investigated SPECT perfusion scans.

  5. Boussignac CPAP system for brain death confirmation with apneic test in case of acute lung injury/adult respiratory distress syndrome – series of cases

    Directory of Open Access Journals (Sweden)

    Wieczorek A

    2015-06-01

    Full Text Available Andrzej Wieczorek,1 Tomasz Gaszynski2 1Department of Anesthesia and Intensive Care, Medical University of Lodz, Lodz, Poland; 2Department of Emergency Medicine and Disaster Medicine, Medical University of Lodz, Lodz, Poland Introduction: There are some patients with severe respiratory disturbances like adult respiratory distress syndrome (ARDS and suspicion of brain death, for whom typical performance of the apneic test is difficult to complete because of quick desaturation and rapid deterioration without effective ventilation. To avoid failure of brain death confirmation and possible loss of organ donation another approach to apneic test is needed. We present two cases of patients with clinical symptoms of brain death, with lung pathology (acute lung injury, ARDS, lung embolism and lung infection, in whom apneic tests for recognizing brain death were difficult to perform. During typical performance of apneic test involving the use of oxygen catheter for apneic oxygenation we observed severe desaturation with growing hypotension and hemodynamic destabilization. But with the use of Boussignac CPAP system all necessary tests were successfully completed, confirming the patient’s brain death, which gave us the opportunity to perform procedures for organ donation. The main reason of apneic test difficulties was severe gas exchange disturbances secondary to ARDS. Thus lack of positive end expiratory pressure during classical performance of apneic test leads to quick desaturation and rapid hemodynamic deterioration, limiting the observation period below dedicated at least 10-minute interval.  Conclusion: The Boussignac CPAP system may be an effective tool for performing transparent apneic test in case of serious respiratory disturbances, especially in the form of acute lung injury or ARDS. Keywords: brain death, organ donor, ARDS, ALI, Boussignac CPAP

  6. Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre-fecal Microbiota Transplantation Evaluation?

    Science.gov (United States)

    Allegretti, Jessica R; Kassam, Zain; Chan, Walter W

    2018-01-01

    Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms. This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm within 90 min. The presence of GI symptoms and CDI resolution were assessed 8 weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical analyses. Twenty recipients (58.3 years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p = 0.09). FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.

  7. Lubiprostone Accelerates Intestinal Transit and Alleviates Small Intestinal Bacterial Overgrowth in Patients With Chronic Constipation.

    Science.gov (United States)

    Sarosiek, Irene; Bashashati, Mohammad; Alvarez, Alicia; Hall, Mark; Shankar, Nagasri; Gomez, Yvette; McCallum, Richard W; Sarosiek, Jerzy

    2016-09-01

    Lubiprostone is an effective treatment for chronic constipation (CC). The mechanism of action of lubiprostone is through increasing fluid secretion and lubrication of the intestinal lumen. The effects of lubiprostone on gastrointestinal transit and small intestinal bacterial overgrowth (SIBO) have not been adequately explored. The current study was designed to investigate whether lubiprostone (1) alters gastrointestinal transit and (2) affects SIBO in patients with constipation. A total of 29 female patients (mean age = 39 years; range: 19-64) with CC received 2 weeks of lubiprostone (24mcg b.i.d., P.O.). Stool consistency based on Bristol stool scale and the frequency of bowel movements (BMs) were recorded. Gastric emptying time, small bowel transit time, colon transit time (CTT), combined small and large bowel transit time (SLBTT) and whole gut transit time were measured using wireless motility capsule. The SIBO status was assessed by the lactulose breath test. Data were analyzed using Wilcoxon rank, Mann-Whitney U, Spearman׳s rank correlation and Chi-square tests. Lubiprostone significantly softened the stool and increased the frequency of BM from median of 2 to 4times per week. The CTT and SLBTT were significantly shorter in responders to lubiprostone (i.e., those with ≥ 2 times increase in the number of their weekly BM) compared with nonresponders. The higher frequency of BM after treatment was significantly correlated with the acceleration of CTT, SLBTT and whole gut transit time. In all, 17 out of 25 (68%) patients, who were tested for SIBO at baseline, were positive. In addition, 7 out of 17 (41%) SIBO-positive patients became SIBO-negative after lubiprostone treatment (P lubiprostone improves the frequency of BMs, softens the stool, accelerates intestinal transit and decreases accompanying SIBO. The improvement of SIBO could be explained by the cleansing effect of increased intestinal fluid and mucus combined with enhanced intestinal motility with

  8. Specific hypermethylation of LINE-1 elements during abnormal overgrowth and differentiation of human placenta.

    Science.gov (United States)

    Perrin, D; Ballestar, E; Fraga, M F; Frappart, L; Esteller, M; Guerin, J-F; Dante, R

    2007-04-12

    In human post-natal somatic cells, low global levels of DNA methylation have been associated with the hypomethylation of several repetitive elements, a feature that has been proposed to be a surrogate epigenetic marker. These data, mainly derived from the analysis of cancer cells, suggest a potential association between loss of cell-growth control and altered differentiation with hypomethylation of repetitive sequences. Partial hydatidiform moles (PHMs) can be used as an alternative model for investigating this association in a non-tumorigenic context. This gestational disease is characterized by abnormal overgrowth and differentiation of the placenta and spontaneous abortion. Here, we comprehensively analyse the DNA methylation of these trophoblastic tissues in both PHM and normal placenta at global and sequence-specific levels. Analysis of the global 5-methylcytosine content and immunohistochemistry indicate that PHM and normal placenta have identical global levels of DNA methylation. In contrast, bisulfite genomic sequencing shows that, whereas Alu, NBL2 and satellite 2 repetitive elements are equally methylated, LINE-1 sequences are hypermethylated in PHM tissues ( approximately 2-fold relative to normal placenta). Interestingly, altered demethylation is also found in triploid diandric embryos that originate from dispermic fertilization of an oocyte, a common event responsible for most PHMs. In conclusion, alterations of DNA methylation do not seem to be randomly distributed in PHM, as several repeated elements remain unaltered, whereas LINE-1 sequences are hypermethylated. In addition, our findings suggest that the hypomethylation of repetitive elements in cancer is directly linked to the neoplasic process and not a simple consequence of loss of growth control observed in most of the cancer cells.

  9. Evaluation of small intestine bacterial overgrowth in patients with functional dyspepsia through H2 breath test

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    Michelle Bafutto Gomes Costa

    2012-12-01

    Full Text Available CONTEXT: Functional dyspepsia is a condition in which symptoms are not related to organic underlying disease; its pathogenesis is not well known. The small intestinal bacterial overgrowth (SIBO is characterized by the increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. The hypothesis of SIBO being associated to functional dyspepsia must be considered, since the impaired motility of the gastrointestinal tract is one of the main etiologic factors involved on both pathologies. OBJECTIVE: To determine if there is SIBO in patients with functional dyspepsia. METHODS: Case-control study, evaluating 34 patients: 23 functional dyspeptic and 11 non-dyspeptic (control group. Questionnaire applied based on Rome III criteria. The patients underwent H2-lactulose breath test, considered positive when: H2 peak exceeding 20 ppm, in relation to fasting, or two peaks exceeding 10 ppm sustained until 60 minutes. RESULTS: Of the 23 dyspeptic patients, 13 (56.5% obtained positive results for SIBO trough the H2-lactulose breath test. On control group, SIBO was not observed. The association between the dyspeptic group and the control group regarding SIBO was statistically significant, with P = 0.0052. In the group of dyspeptic patients, 12 (52.2% were using proton pump inhibitor; of these 9 (75% were positive for SIBO. In the control group, none of the 11 patients used proton pump inhibitors and SIBO was not observed. The association of the dyspeptic group using proton pump inhibitor that were positive for SIBO and the control group was statistically significant, with P = 0.0011. CONCLUSION: It was found that, patients with functional dyspepsia presented SIBO, when they underwent to H2-lactulose breath test, compared to the non-dyspeptic. In addition, it was observed a higher prevalence of SIBO in dyspeptic patients that were using proton pump inhibitors, compared to control group.

  10. Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

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    Reinshagen Max

    2009-07-01

    Full Text Available Abstract Background Small intestinal bacterial overgrowth (SIBO is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients. Methods One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT. Results Thirty-eight patients (25.3% were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003 and lower body weight (63.6 vs 70.4 kg, p = 0.014. There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neoterminal ileum again showed only tendential association with the development of SIBO. Conclusion SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors.

  11. Doom and boom on a resilient reef: climate change, algal overgrowth and coral recovery.

    Directory of Open Access Journals (Sweden)

    Guillermo Diaz-Pulido

    Full Text Available BACKGROUND: Coral reefs around the world are experiencing large-scale degradation, largely due to global climate change, overfishing, diseases and eutrophication. Climate change models suggest increasing frequency and severity of warming-induced coral bleaching events, with consequent increases in coral mortality and algal overgrowth. Critically, the recovery of damaged reefs will depend on the reversibility of seaweed blooms, generally considered to depend on grazing of the seaweed, and replenishment of corals by larvae that successfully recruit to damaged reefs. These processes usually take years to decades to bring a reef back to coral dominance. METHODOLOGY/PRINCIPAL FINDINGS: In 2006, mass bleaching of corals on inshore reefs of the Great Barrier Reef caused high coral mortality. Here we show that this coral mortality was followed by an unprecedented bloom of a single species of unpalatable seaweed (Lobophora variegata, colonizing dead coral skeletons, but that corals on these reefs recovered dramatically, in less than a year. Unexpectedly, this rapid reversal did not involve reestablishment of corals by recruitment of coral larvae, as often assumed, but depended on several ecological mechanisms previously underestimated. CONCLUSIONS/SIGNIFICANCE: These mechanisms of ecological recovery included rapid regeneration rates of remnant coral tissue, very high competitive ability of the corals allowing them to out-compete the seaweed, a natural seasonal decline in the particular species of dominant seaweed, and an effective marine protected area system. Our study provides a key example of the doom and boom of a highly resilient reef, and new insights into the variability and mechanisms of reef resilience under rapid climate change.

  12. Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome

    Directory of Open Access Journals (Sweden)

    J. Hsiao

    2016-07-01

    Full Text Available Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT. Using oligonucleotide-based compounds (AntagoNATs targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

  13. Organic brain syndrome

    Science.gov (United States)

    ... the disorder, but may include: Blood tests Electroencephalogram (EEG) Head CT scan Head MRI Lumbar puncture (spinal ... 5th ed. Philadelphia, PA: Elsevier; 2014:chap 61. Review Date 2/27/2016 Updated by: Amit M. ...

  14. Brain Fag Syndrome

    African Journals Online (AJOL)

    1Department of Psychiatry, Lagos State University College of Medicine,Ikeja. Lagos ... However, its course, response to treatment and outcome deserve .... COSb – Cultural Orientation Scale; SSSc – Student Stress Scale; GSSd – General ...

  15. White matter alterations in the brains of patients with active, remitted, and cured cushing syndrome: a DTI study.

    Science.gov (United States)

    Pires, P; Santos, A; Vives-Gilabert, Y; Webb, S M; Sainz-Ruiz, A; Resmini, E; Crespo, I; de Juan-Delago, M; Gómez-Anson, B

    2015-06-01

    Cushing syndrome appears after chronic exposure to elevated glucocorticoid levels. Cortisol excess may alter white matter microstructure. Our purpose was to study WM changes in patients with Cushing syndrome compared with controls by using DTI and the influence of hypercortisolism. Thirty-five patients with Cushing syndrome and 35 healthy controls, matched for age, education, and sex, were analyzed through DTI (tract-based spatial statistics) for fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity (general linear model, family-wise error, and threshold-free cluster enhancement corrections, P Cushing syndrome with active hypercortisolism, 7 with Cushing syndrome with medication-remitted cortisol, 20 surgically cured, and 35 controls. Cardiovascular risk factors were used as covariates. In addition, correlations were analyzed among DTI values, concomitant 24-hour urinary free cortisol levels, and disease duration. There were widespread alterations (reduced fractional anisotropy, and increased mean diffusivity, axial diffusivity, and radial diffusivity values; P Cushing syndrome compared with controls, independent of the cardiovascular risk factors present. Both active and cured Cushing syndrome subgroups showed similar changes compared with controls. Patients with medically remitted Cushing syndrome also had reduced fractional anisotropy and increased mean diffusivity and radial diffusivity values, compared with controls. No correlations were found between DTI maps and 24-hour urinary free cortisol levels or with disease duration. Diffuse WM alterations in patients with Cushing syndrome suggest underlying loss of WM integrity and demyelination. Once present, they seem to be independent of concomitant hypercortisolism, persisting after remission/cure. © 2015 by American Journal of Neuroradiology.

  16. Proteus syndrome: a case report and a case study review in China

    Directory of Open Access Journals (Sweden)

    Xi-Bao Zhang

    2010-02-01

    Full Text Available Proteus syndrome (PS is a rare and sporadic disorder characterized by overgrowth of multiple tissues and a propensity to develop particular neoplasms. The clinical manifestations of PS include macrodactyly, vertebral abnormalities, asymmetric limb overgrowth and length discrepancy, hyperostosis, abnormal and asymmetric fat distribution, asymmetric muscle development, connective tissue nevi, and vascular malformations. We report a 16-year old female patient who manifested a number of these complications and review the Chinese literature about the diagnosis, natural history, and management of PS.

  17. A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome

    Science.gov (United States)

    Steinhoff, Nikolaus; Heine, Astrid M.; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

    2015-01-01

    The global cerebral network allows music “ to do to us what it does.” While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research. PMID:26347603

  18. A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome.

    Science.gov (United States)

    Steinhoff, Nikolaus; Heine, Astrid M; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

    2015-01-01

    The global cerebral network allows music " to do to us what it does." While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research.

  19. A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome

    Directory of Open Access Journals (Sweden)

    Nikolaus eSteinhoff

    2015-08-01

    Full Text Available The global cerebral network allows music to do to us what it does. While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people.Therefore, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS during MT. Each patient had three PET investigations: (i during a resting state, (ii during the first exposure to MT, and (iii during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week, while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34% than in the control group after five weeks. The preliminary results suggest that MT activates the three brain regions described above.In this article, we present our approach to the neuroscience of music therapy and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research.

  20. Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells.

    Directory of Open Access Journals (Sweden)

    Mark D Grier

    Full Text Available Angelman Syndrome (AS is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. While imprinting in neurons of the brain has been well described, the imprinting and expression of Ube3a in other neural tissues remains relatively unexplored. Moreover, given the overwhelming deficits in brain function in AS patients, the possibility of disrupted Ube3a expression in the infratentorial nervous system and its consequent disability have been largely ignored. We evaluated the imprinting status of Ube3a in the spinal cord and sciatic nerve and show that it is also imprinted in these neural tissues. Furthermore, a growing body of clinical and radiological evidence has suggested that myelin dysfunction may contribute to morbidity in many neurodevelopmental syndromes. However, findings regarding Ube3a expression in non-neuronal cells of the brain have varied. Utilizing enriched primary cultures of oligodendrocytes and astrocytes, we show that Ube3a is expressed, but not imprinted in these cell types. Unlike many other neurodevelopmental disorders, AS symptoms do not become apparent until roughly 6 to 12 months of age. To determine the temporal expression pattern and silencing, we analyzed Ube3a expression in AS mice at several time points. We confirm relaxed imprinting of Ube3a in neurons of the postnatal developing cortex, but not in structures in which neurogenesis and migration are more complete. This furthers the hypothesis that the apparently normal window of development in AS patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development.